DYSLIPIDEMIA

BACKGROUND

The lipids that are commonly measured in blood include various forms of cholesterol, as well as triglycerides. High-density lipoprotein (HDL) is the “good cholesterol,” and higher levels reduce the risk of cardiovascular disease. Low-density lipoprotein (LDL) is the “bad cholesterol,” linked to increased risk of heart attacks and strokes. High triglycerides are also a risk factor for cardiovascular disease.

In dyslipidemia, the level of one or more of these lipids is abnormal (either too high or too low). Increased activity and a healthy diet should be the first course of treatment for dyslipidemia. If you are at risk for heart attack or stroke, and diet and exercise fail to bring high lipid levels into the healthy range, your doctor may recommend taking a lipid-lowering medicine.

LIPID TYPES

There are many different types of lipid (also called lipoproteins). Blood tests can measure the level of your lipoproteins. The standard lipid blood tests include a measurement of total cholesterol, LDL (low density lipoproteins) and HDL (high density lipoproteins), and triglycerides.

TOTAL CHOLESTEROL: A high total cholesterol level can increase your risk of cardiovascular disease. However, decisions about when to treat high cholesterol are usually based upon the level of LDL or HDL cholesterol, rather than the level of total cholesterol.

• A total cholesterol level of less than 200mg / dL (5.17 mmol / L) is normal.
• A total cholesterol level of 200 to 239mg / dL (5.17 to 6.18 mmol/L) is borderline high.
• A total cholesterol level greater than or equal to 240mg/dL (6.21 mmol/L) is high.

The total cholesterol level can be measured any time of day. It is not necessary to fast (avoid eating for 12 hours) before testing.

LDL CHOLESTEROL: Some health care providers make decisions about how to treat lipids based on the low density lipoprotein (LDL) cholesterol (sometimes called "bad cholesterol"). Higher LDL cholesterol levels increase your risk of cardiovascular disease. If your health care provider uses this strategy, your goal LDL cholesterol will depend on several factors, including any history of cardiovascular disease and your risk of developing cardiovascular disease in the future. People at higher risk are often assigned a lower LDL cholesterol goal.

In many cases, your LDL-cholesterol can be measured even after you have eaten recently.

TRIGLYCERIDES: High triglyceride levels are also associated with an increased risk of cardiovascular disease, although this association is not typically important once other risk factors are taken into account. Triglyceride levels are divided as follows:

• Normal - less than 150mg / dL (1.69 mmol / L)
• Borderline high - 150 to 199mg / dL (1.69 to 2.25 mmol / L)
• High - 200 to 499mg / dL (2.25 to 5.63 mmol / L)
• Very high - greater than 500mg / dL (5.65 mmol / L)

Triglycerides should be measured after fasting for 12 to 14 hours.

HDL CHOLESTEROL: Not all cholesterol is bad. Elevated levels of HDL cholesterol actually lower the risk of cardiovascular disease. A level greater than or equal to 60 mg / dL or 1.55 mmol / L is excellent, while levels of HDL cholesterol less than 40 mg / dL or 1.03 mmol / L are lower than desired. There are no treatments for raising HDL cholesterol that has been proven to reduce the risk of heart attacks and strokes.

Similar to total cholesterol, the HDL-cholesterol can be measured on any blood specimen. It is not necessary to be fasting.

NON-HDL CHOLESTEROL: Non-HDL cholesterol is calculated by subtracting HDL cholesterol from total cholesterol. Since total cholesterol and HDL cholesterol can be measured without fasting, so can non-HDL cholesterol. Non-HDL cholesterol is a good predictor of cardiovascular risk and is a better predictor of risk than LDL cholesterol in people with type 2 diabetes and in women.

DISEASE OCCURRENCE IN POPULATION

The World Health Organization estimates that dyslipidemia is associated with more than half of global cases of ischemic heart disease and more than 4 million deaths per year.

A study among rural adults in Pakistan (n = 1658), reported the prevalence of hypercholesterolemia, hypertriglyceridemia, low HDL-C (high-density lipoproteins cholesterol) and high LDL-C (high-density lipoproteins cholesterol) as 30.6%, 29.4%, 79.6% and 41.2% respectively. A survey in Pakistan revealed that a large proportion of the population had lipid abnormalities and females had significantly greater values of total cholesterol.

RISK FACTORS

TYPE 2 DIABETES MELLITUS: The number of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) particles increase with increasing insulin resistance, while HDL particle concentration decreases.

EXCESSIVE ALCOHOL CONSUMPTION: While moderate alcohol consumption generally has favorable effects on lipids, excessive alcohol consumption can raise triglyceride levels. This is particular concern in patients with severe hypertriglyceridemia at baseline.

CHOLESTATIC LIVER DISEASES: Primary biliary cholangitis and similar disorders may be accompanied by marked hypercholesterolemia. Clinical finding include xanthomata striata palmare that may appear when the serum cholesterol concentration is 1400 mg / dL (36 mmol /L) or higher. Xanthomata appear on the extremities as well. A xanthoma is a deposition of yellowish cholesterol-rich material that can appear anywhere in the body in various disease states.

NEPHROTIC SYNDROME: Marked hyperlipidemia can occur in the nephrotic syndrome due primarily to high serum total and low density lipoprotein (LDL) cholesterol concentrations.

CHRONIC KIDNEY DISEASE: Dyslipidemia is less prominent in chronic kidney disease (CKD), but CKD is associated with elevations in low density lipoprotein (LDL) cholesterol and triglycerides, and low levels of high density lipoprotein (HDL) cholesterol; hypertriglyceridemia (type IV hyperlipoproteinemia) occurs in 30 to 50 percent of cases of CKD.

HYPOTHYROIDISM: Hypothyroidism is frequently associated with and is a common cause of hyperlipidemia.

CIGARETTE SMOKING: Smoking modestly lowers the serum high density lipoprotein (HDL) cholesterol concentrations and may induce insulin resistance. Cigarette smoking impairs HDL function by reducing antioxidant and anti-inflammatory capacity and impeding cellular cholesterol efflux.

OBESITY: Obesity is associated with a number of deleterious changes in lipid metabolism, including high serum concentrations of total cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, and triglycerides, and a reduction in serum high density lipoprotein (HDL) cholesterol concentration of about 5 percent.

DRUGS: Some medications, including thiazide diuretics, beta blockers, and oral estrogens can cause modest changes in serum lipid concentrations. Some of the atypical antipsychotic agents, in particular, clozapine and olanzapine, have been associated with weight gain, obesity, hypertriglyceridemia, and development of diabetes mellitus (DM). The mechanism(s) by which they cause the metabolic syndrome have not been defined.

Other risk factors include:

• Irregular or absence of exercise
• Hypertension (people with hypertension include those with a blood pressure at or above140 / 90 mm of Hg and those who use blood pressure medication)
• Family history of coronary disease in a parents or sibling
• Gender: Men have a higher risk of cardiovascular disease than women at every age.
• Age: There is an increasing risk of cardiovascular disease with increasing age.

SIGN AND SYMPTOMS

Dyslipidemia itself usually causes no symptoms but can lead to symptomatic vascular disease, including coronary artery disease (CAD), stroke, and peripheral arterial disease.

Some of the common symptoms that may be encountered in relation to dyslipidemia may include the following:

• Corneal opacificationis among the ocular findings that may be exhibited to people with dyslipidemia. Corneal opacities can lead to scarring or clouding of the cornea, which decreases vision.
• Corneal Arcusis also among the ophthalmologic sign that may be exhibited by a person with dyslipidemia. Arcus is a deposition of lipid in the part of eye called as corneal stroma.
• Severe hypertriglyceridemia (>2000 mg / dL [> 6 mmol / L]) can give retinal arteries and veins a creamy white appearance (lipemia retinalis).
• When lipid levels are exceedingly high, cholesterol may be deposited (xanthomas) in tendons or just beneath the skin under the eyes. Patients with severe elevations of Triglycerides (TGs) can have eruptive xanthomas over the trunk, back, elbows, buttocks, knees, hands, and feet.
• High levels of Triglycerides (>1000 mg / dL [> 3 mmol / L]) can cause acute pancreatitis.

OTHER SYMPTOMS:

Other signs and symptoms may also include the following:

• Balance impairment
• Pain in the calf when walking
• Dizziness
• Abdominal pain
• Confusion
• Difficulty in speaking
• Paresthesias
• Dypsnea

After a prolonged period, following conditions may appear:

• Coronary artery disease (CAD)
• Ischemic heart disease
• Peripheral vascular disease
• Stroke
• Cerebrovasular disease and kidney disease

DIAGNOSTIC TEST

Lipid Profile: Screening for hyperlipidemia is done with a blood test called a lipid profile. TC, TGs, and HDL cholesterol are measured directly. TC and HDL cholesterol can be measured in the non-fasting state, but most patients should have all lipids measured while fasting (usually for 12 h) for maximum accuracy and consistency.

OTHER TESTS:

• Patients with premature atherosclerotic cardiovascular disease, with normal or near-normal lipid levels, or high LDL levels refractory to drug therapy should probably have Lipoprotein Lp(a) levels measured. Lp(a) may also be directly measured in patients with borderline high LDL cholesterol levels to determine whether drug therapy is warranted.
• C-reactive protein may be considered in the same populations.
• Measurements of LDL particle number or apoprotein B-100 (apo B) may be useful in patients with elevated TGs and the metabolic syndrome.

TEST FOR SECONDARY CAUSES: Tests for secondary causes of dyslipidemia including measurements of fasting glucose, liver enzymes, creatinine, thyroid-stimulating hormone (TSH), and urinary protein, should be done in most patients with newly diagnosed dyslipidemia and when a component of the lipid profile has inexplicably changed for the worse.

UNIVERSAL SCREENING: Universal screening using a fasting lipid profile (TC, TGs, HDL cholesterol, and calculated LDL cholesterol) should be done in all children between age 9 and 11 (or at age 2 if children have a family history of severe hyperlipidemia or premature CAD). The National Cholesterol Education Program (NCEP) recommends that all adults 20 years and older obtain a fasting lipid profile, a blood test that measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides—at least every 5 years. Those with known risk factors, such as diabetes or a family history of CHD, may need to be screened more frequently.

TREATMENT OPTIONS

Lipid levels can be lowered with lifestyle changes, medications, or a combination of these approaches.

LIFESTYLE CHANGES: All patients with dyslipidemia should try to make some changes in their day-to-day habits, by reducing total and saturated fat in the diet, losing weight (if overweight or obese), performing aerobic exercise, and eating a diet rich in fruits and vegetables. Quitting smoking may raise levels of “good” HDL cholesterol. Soluble fiber has been shown to modestly reduce total cholesterol and LDL cholesterol levels.

The benefits of such lifestyle modifications usually become evident within 6 to 12 months. However, the success of lipid lowering with lifestyle modification varies widely, and healthcare providers sometimes elect to begin drug therapy before this time period is over.

MEDICATIONS: There are many medications available to help lower elevated levels of LDL cholesterol and triglycerides, but only a few for increasing HDL cholesterol. Each category of medication targets a specific lipid and varies in how it works, how effective it is, and how much it costs. Your healthcare provider will recommend a medication or combination of medications based on blood lipid levels and other individual factors.

STATINS: Statins are among the most powerful drugs for lowering LDL cholesterol and are the most effective drugs for prevention of coronary heart disease, heart attack, stroke, and death. Statins include lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, and rosuvastatin. These medications decrease the body's production of cholesterol and can reduce LDL levels by as much as 20 to 60 percent. In addition, statins can lower triglycerides and slightly raise HDL cholesterol levels. Statins may prevent heart attacks and strokes in more ways than just lowering cholesterol levels. For instance, statins seem to help keep buildups in blood vessels (known as plaques) from rupturing. Plaque rupture is an important event that can lead to a heart attack.

It is important to closely follow the dosing instructions for when to take statins; some are more effective when taken before bedtime while others should be taken with a meal.

In addition, some foods, such as grapefruit or grapefruit juice, can increase the risk of side effects of statins. Most manufacturers recommend that people who take lovastatin, simvastatin, or atorvastatin consume no more than one-half of a grapefruit or 8 ounces of grapefruit juice per day.

PCSK9 INHIBITORS: PCSK9 inhibitors are a newer class of drug that can also lower LDL cholesterol levels. Drugs in this class can also lower levels of other lipoproteins, such as lipoprotein(a), that can cause buildup of blood vessel plaques. The PCSK9 inhibitors include alirocumab and evolocumab, which are given by injection every two to four weeks. They have been shown to reduce LDL cholesterol by as much as 70 percent, and by as much as 60 percent in patients who are also on statin therapy. Experience with these drugs is limited and more study is needed to understand the longer-term effects; however, it appears that they can substantially reduce cardiovascular events (such as heart attack or stroke) and mortality.

EZETIMIBE: Ezetimibe impairs the body's ability to absorb cholesterol from food as well as cholesterol that the body produces internally. It lowers LDL cholesterol levels and has relatively few side effects. When used in combination with a statin in treatment after an acute coronary syndrome (e.g. heart attack), ezetimibe provides a small additional reduction in cardiovascular events.

BILE ACID SEQUESTRANTS: The bile acid sequestrants include cholestyramine, colestipol, and colesevelam. These medications bind to bile acids in the intestine, reducing the amount of cholesterol absorbed from foods.

Bile acid sequestrants may be recommended to treat mild to moderately elevated LDL cholesterol levels. However, side effects can be bothersome, and may include nausea, bloating, cramping, and liver injury.

Bile acid sequestrants can interact with some medications, including as digoxin and warfarin, and with the absorption of fat-soluble vitamins (including vitamins A, D, K, and E). Taking these medications at different times of day can solve these problems in some cases.

NICOTINIC ACID (NIACIN): Nicotinic acid is a vitamin that is available in immediate-release, sustained-release, and extended-release formulations. Nicotinic acid may be recommended for people with elevated cholesterol levels that do not respond adequately despite maximum tolerated dosages of statins and for people with some types of familial hyperlipidemia, particularly those with high lipoprotein(a) levels. However, most patients taking statins should not take nicotinic acid.

SIDE EFFECTS: Nicotinic acid has several possible side effects, including flushing (when the face or body turns red and becomes warm), itching, nausea, and numbness and tingling. This medication can also injure the liver; patients who use it require regular monitoring of liver function.

The immediate-release formulation is more likely to produce side effects, but is also more effective at lowering cholesterol levels and less likely to injure the liver than certain sustained-release formulations. The sustained-release and extended-release formulations have fewer side effects. Nicotinic acid should be taken with food or shortly after ingesting the largest meal of the day.

FIBRATES: Fibrate medications (gemfibrozil, fenofibrate and fenofibric acid) can lower triglyceride levels and raise HDL cholesterol levels.

Fibrates may be recommended for people with elevated triglyceride and cholesterol levels. Fibrates have been associated with muscle toxicity (causing muscle pain or weakness), especially when used by people with kidney insufficiency or when used in combination with a statin medication. Fenofibrate / fenofibric acid are less likely to interact with statins than gemfibrozil, and are safer in people who must use both medications.

PLASMAPHERESIS: In rare patients with extremely high cholesterol levels (familial hypercholesterolemia), repeated removal of blood plasma (plasmapheresis) may be recommended to lower blood cholesterol levels.

NUTRITIONAL SUPPLEMENTS

FISH OIL: Oily fish, such as mackerel, herring, bluefish, sardines, salmon, and anchovies, contain two important fatty acids, called eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Eating a diet that includes one to two servings of oily fish per week can reduce triglyceride levels and reduce the risk of death from coronary heart disease. Fish oil supplements are believed to have the same benefit. A daily 1 gram fish oil supplement may be recommended if you do not eat enough fish.

SOY PROTEIN: Soy protein contains isoflavones, which mimic the action of estrogen. A diet high in soy protein can slightly lower levels of total cholesterol, LDL cholesterol, and triglycerides, and raise levels of HDL cholesterol. However, normal protein should not be replaced with soy protein or isoflavone supplements in an effort to lower cholesterol levels.

GARLIC: A large trial showed that garlic is not effective in lowering cholesterol. In this study, participants with an elevated LDL took one of several types of garlic extract (raw, powdered, aged) or a placebo (inactive pill) six days per week for six months. At the end of the study, the LDL levels were not improved in the garlic group compared to the group that took the placebo. We do not recommend garlic to lower cholesterol.

PLANT STANOLS AND STEROLS: Plant stanols and sterols may act by blocking the absorption of cholesterol in the intestine. They are naturally found in some fruits, vegetables, vegetable oils, nuts, seeds, and legumes.

STICKING WITH TREATMENT: The treatment of high cholesterol and / or triglycerides is a lifelong process. Although medications can rapidly lower your levels, it often takes 6 to 12 months before the effects of lifestyle modifications are noticeable. Once you have an effective treatment plan and you begin to see results, it is important to stick with the plan. Stopping treatment usually allows lipid levels to rise again.

Most people who stop treatment do so because of side effects. However, there are a wide variety of medications available today, which should make it possible for most people to find an option that works for them. Talk with a healthcare provider if a specific medication is not working; he or she can recommend alternatives that are compatible with your lifestyle and beliefs.

PRECAUTIONS
Diet suggestions: It is not necessary to follow a low-fat diet but rather reduce the intake of saturated fat, trans fats, and cholesterol. The diet should consist of a colorful array of whole fruits and vegetables, be high in fiber, and whole grains.
Fast foods, high carbohydrate foods, and any foods that do not offer good nutritional value should be restricted or eliminated.

Regular servings of fish, nuts, and legumes are recommended. When oil is used, it should be olive or another monounsaturated oil. Eat foods high in soluble fiber such as oats, beans, peas and certain fruits.
Weight: Being overweight is a risk factor for dyslipidemia and heart disease. Losing weight can help lower your LDL, total cholesterol, and lower your triglyceride levels. It can also raise your HDL, which helps to remove the bad cholesterol out of the blood.
Physical activity: Not being physically active is a risk factor for heart disease. Regular exercise and activity can help lower LDL (bad) cholesterol and raise HDL (good) cholesterol levels. It also helps you lose weight. You should try to be physically active for 30 minutes at least 5 days a week. Brisk walking is an excellent and easy choice for exercise.
No smoking: Smoking activates many problems that contribute to heart disease. It promotes plaque buildup on the walls of the arteries, increases the bad cholesterol, and encourages blood clot formations and inflammation. Quitting smoking will result in increases in HDL, which may be part of the reduced cardiovascular disease risk seen after smoking cessation.

RESTRICT ALCOHOL CONSUMPTION: Moderate alcohol consumption increases levels of HDL cholesterol, which decreases the risk of CHD. However, chronic, heavy alcohol use raises triglyceride levels, and is associated with many other harmful effects. Therefore, it is recommended that, on average, women consume no more than one alcoholic beverage per day; men should consume no more than two alcoholic drinks daily. (A drink is considered one 12-ounce beer, 4 ounces of wine, or 1.5 ounces of 80-proof spirits.)

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