Dyslipidemias are a key
risk factor in people with the metabolic syndrome and contribute significantly
towards the long term risk for premature and accelerated atherosclerosis.
Lipid disorders are also seen in many people with diabetes and are a major
factor in the microvascular and especially in the macrovascular diabetic
The dyslipidemias merit rigorous and aggressive correction.
The major dyslipidemias are:
1) Increased levels of low density lipoprotein
2) Atherogenic dyslipidaemia describes
a combination of
Increased serum triglycerides (TG);
Increased VLDL particle number;
Increased levels of small dense LDL-C particles;
Increased levels of apolipoprotein B (ApoB);
(The increased number of VLDL and LDL
particles accounts for the increased level of total apo B).
Decreased levels of HDL-C particles,
All of these are atherogenic by themselves,
but their atherogenicity is significantly increased when present in combination.
Athergenic dyslipidemia is commonly observed in patients with both type
2 diabetes and the metabolic syndrome.
The latest recommendations
state that in adults with diabetes, the optimal LDL-C level is less than
100 mg/dl (in patients with additional risks, the target has been brought
down to 70mg/dl; High-risk patients are those with established ASCVD,
diabetes, or 10-year risk for coronary heart disease >20%. For cerebrovascular
disease, high-risk condition includes transient ischemic attack or stroke
of carotid origin or >50% carotid stenosis.) and the optimal HDL-C
level is more than 40mg/dl in men and 50mg/dl in women; triglyceride levels
should be less than 150 mg/dl;.
EVERY 1% REDUCTION IN
THE LEVELS OF T-C, LOWERS THE RISK FOR CAD BY 2%!
According to ATP III, atherogenic dyslipidemia
can become a target for lipid-lowering therapy after the goal for LDL-C
has been attained. In other words, as long as LDL-C remains above goal
level, LDL-C is the primary target of therapy even in the metabolic syndrome.
Other lipid risk factors are secondary. The LDL-C goals depend on estimates
of absolute risk.
In patients with atherogenic dyslipidemia
in whom serum triglyceride levels are 200 mg/dL, non-HDL-C becomes the
next target of treatment after the LDL-C goal is reached.
If the serum triglyceride levels are significantly raised (>500mg/dl),
then lowering these levels should take precedence even over lowering the
Raising HDL-C becomes a tertiary aim.
In practice, all the lipid abnormalities
are managed together rather than in sequence.
Where only lipid levels
are abnormal, lifestyle intervention should be undertaken first.
Beyond weight control and
reduction of total calories, the diet should be low in saturated fats,
trans fats, cholesterol, sodium, and simple sugars. In addition, there
should be ample intakes of fruits, vegetables, and whole grains;
Very high carbohydrate intakes can exacerbate the dyslipidemia of the
Diet therapy is important in optimizing lipid levels. Total fat intake
should be restricted to 25-30% of total calorie intake. It is essential
to take into account "invisible" fat in the food.
Ensure correct essential fatty acid (EFA) intake, with near optimal omega
6 / omega 3 (w6/w3) ratio (5:1).
Cooking oils should be a judicious mix of PUFAs, MUFAS and saturated fats;
no one oils is beneficial; cooking oils should contribute <6% total
Foods rich in saturated fats and high in n6 fatty acids should be reduced.
Foods rich in n3 fatty acids may be beneficial.
Many of these aspects have been discussed
in detail in the section dealing with diet and exercise
Increases in daily routine
activities and a regular exercise regimen is necessary and must be encouraged.
Many of these aspects have been discussed in detail in the section
dealing with diet and exercise
Rigorous management of other associated disorders such as obesity, hypertension,
impaired glycemia and diabetes.
Smoking intake to be actively discouraged.
Rule out other secondary causes of dyslipidemias
For a list of some common secondary causes of dyslipidemias other than
diabetes, see Appendix 13 a
|DIET AND LIFESTYLE MODIFICATIONS
SHOULD BE GIVEN AN ADEQUATE TRIAL BEFORE COMMENCING LIPID LOWERING
DRUG THERAPY UNLESS THERE ARE DEFINITE INDICATIONS WHICH NECESSITATE
IMMEDIATE STARTING OF THE DRUGS .
Drugs Affecting Lipoprotein
||Agents and Daily Doses
||Common Side Effects
|HMG CoA reductase inhibitors (statins)
||Lovastatin (20-80 mg), pravastatin (20-40 mg), simvastatin (20-80
mg), fluvastatin (20-80 mg), atorvastatin (10-80 mg)Rosuvastatin (10-40mg)
Statins, except atorvastatin, are usually dosed at night because of
higher nocturnal cholesterol synthesis.
|MyopathyIncreased liver enzymes
Active or chronic liver disease Relative:
Concomitant use of certain drugs and/or the presence of certain other
|Bile acid sequestrants
||Cholestyramine (4-16 g)Colestipol (5-20 g)Colesevelam (2.6-3.8 g)
||GI distressConstipationDecreased absorption of other drugs
TG > 400 mg/dL Relative:
TG > 200 mg/dL
||Immediate release (crystalline) nicotinic acid (1.5-3 gm),
Extended release nicotinic acid (1-2 g),
Sustained-release nicotinic acid (1-2 g)
|Flushing HyperglycemiaHyperuricemia (or gout)Upper GI distressHepatotoxicity
Chronic liver disease
Severe gout Relative:
Peptic ulcer disease
||Gemfibrozil (600 mg twice a day)Fenofibrate (200 mg)Clofibrate (1000
mg twice a day)
Severe renal disease
||10mg a day
||Abdominal pain, back pain, diarrhea, joint pain, sinusitis, headache,
dizziness, diarrhea, sore throat, runny nose, sneezing, Rarely myopathy,
||Moderate to severe liver disease, Allergic reactions; Not for children
* Some commonly used medications
or consumption of alcohol, etc. and the presence of ceratin factors can
increase the risk for statin induced myopathy and should be kept in mind
when prescribing these drugs.
For a list of such drugs and and other factors which may increase the
risk of statin associated myopathy see Appendix 13b
A practical approach to the pharmacologic treatment of lipid disorders
Abbreviations: LDL, Low-density lipoprotein; HDL, high-density lipoprotein;
TG, triglyceride; TZDs, thiazolidinediones.
In general, therapy is started with a statin although when triglycerides
are 500 mg/dL, triglyceride-lowering drugs should be considered alongside
to prevent the development of acute pancreatitis.
Statins reduce all ApoB-containing lipoproteins and help to achieve the
LDL-C as well as for non-HDL-C goals.
If non-HDL-C remains elevated after the LDL-C goal is reached:
- Increase the statin dose further. Statins
lower both LDL-C and non-HDL-C and in addition, reduce risk for ASCVD
events in patients with the metabolic syndrome.
- Add a fibrate and if necessary nicotinic
acid to the statin. Both fibrates and nicotinic acid reduce non-HDL-C
and reportedly decrease risk for ASCVD in patients with the metabolic
syndrome/type 2 diabetes mellitus.
If the Tg levels are relatively
high, it may be better to start therapy with a statin and a fibrate.
If the HDL-C levels are low, combining a fibrate or nicotinic acid with
LDL-C-lowering treatment becomes an option. Both fibrates and nicotinic
acid raise HDL-C as well as reduce triglycerides and small LDL particles.
Patients with IFG, IGT, or diabetes who are treated with nicotinic acid
deserve careful monitoring for worsening of hyperglycemia. Lower doses
of nicotinic acid lessen this risk.
If a fibrate or nicotinic acid is used with a statin, higher doses of
the statin generally should be avoided to minimize risks for myopathy
or hepatic effects.
|Although many of
the drugs are started as monotherapy, in most patients with the metabolic
syndrome or established T2DM it may be necessary to use combination
therapies to reach the targeted levels.
For Changes in Serum
Lipid Values with Different Classes of lipid lowering drugs, see Appendix