Diabetes, Cholesterol and the Statins

Cardiovascular disease, or CVD, is the leading cause of death among Type 2 diabetics living in the United States.

CVD is a general term which refers to people with blockage of the heart’s blood vessels (also known as coronary artery disease or CAD), blockage in the vessels of the leg (peripheral vascular disease or PVD), and blockage of the carotid arteries (the blood vessels supplying the brain).

Diabetes alone is a risk factor for CVD, increasing your risk 2-4 fold.

Another very important risk factor for cardiovascular disease is your LDL cholesterol.

When your doctor tells you he/she is obtaining a blood sample to “check your cholesterol” or “measure your lipids”, they may check your total cholesterol, LDL cholesterol, HDL cholesterol and total triglycerides.

If all four measurements are included, it is called the “lipid profile”.

The blood test is typically obtained after an 8-12 hour overnight fast.

Although the LDL and HDL cholesterol may be further divided into sub-fractions (basically good and bad subtypes of the LDL and HDL), this level of sophisticated testing is rarely performed.

Given the association of elevated LDL-cholesterol (or LDL-c) levels and CVD, LDL is known as the “bad cholesterol”.

Since diabetes alone is a risk factor for CVD, the LDL-c goals are lower in diabetics.

In diabetics without known CVD, the goal LDL-c is <100 mg/dl (2.6 mmol/l). In a non-diabetic without known CVD, the goal LDL-c is <130 (3.4 mmol/l)

In diabetics with documented CVD, the goal LDL-c is typically <70 mg/dl (1.8 mmol/l).

Unless a person already has clinical evidence of CVD, or has cholesterol levels which are markedly elevated, lifestyle modifications are the first step in the management of an elevated LDL-c.

If lifestyle changes aren’t successful, medications are initiated.

The timing between the initiation of lifestyle changes and medical therapy will vary for each person, but is typically 90 days.

Statins are the most common class of drugs used to lower LDL cholesterol levels.

Available statins include simvastatin (Zocor), atorvastatin (Lipitor), lovastatin (Mevacor), pravastatin (Pravachol), atorvastatin (Lipitor) and rosuvastatin (Crestor).

Except for rosuvastatin, all statins are available as generics.

The statins work by inhibiting HMG-CoA reductase. This is an enzyme which is important in cholesterol synthesis.

Inhibition of the enzyme leads to an increased number of LDL receptors on the liver cells.

This leads to increased clearance of LDL from the circulation, and lower LDL-c levels in the blood.

All statins will:

1)Reduce LDL-c levels significantly

Atorvastatin and Rosuvastatin appear to be most effective at LDL-c reduction with a 51-55% reduction at maximum doses.

For every 39 mg/dl your LDL-c is lowered, your risk of a major CVD event is reduced 25%.

LDL-c lowering is dose dependent.

2)Lower triglyceride levels modestly

Atorvastatin and Rosuvastatin appear to be most effective with an 18%-28% reduction.

Triglyceride benefits are most significant if you have high baseline triglycerides.

3)Raise HDL-c levels mildly

Your HDL-c levels are typically raised 5-10% with statins.

Simvastatin 40 mg appears to be the most effective

Additional beneficial effects may include reduced inflammation, stabilization of atherosclerotic plaques (the build-up of cholesterol in the blood vessels), and reduction of clot size.

Although statins are safe, side effects may occur.

These include:

1)Muscle-related side effects

Muscle pain is one of the most common complaints among statin users.

The estimated prevalence of this complaint is 2-10%.

Symptoms are most common during the first months of therapy, but may occur at any time.

Higher statin doses are associated with a greater risk of muscle symptoms.

Lower statin doses, or alternate day dosing, may reduce muscle related complaints.

Changing the statin brand may also eliminate symptoms.

In the majority of people, discontinuation of the statin will result in resolution of all muscle related complaint.s

Although some people believe adding coenzyme-Q will prevent or reduce muscle symptoms (the rationale is that statins lower coenzyme-Q levels), studies supporting this are conflicting.

“Myopathy” is typically defined as a >10x increase in muscle enzymes (CPK) associated with muscle weakness and pain.

Among current statins, the risk of myopathy ranges from 1.6-3.4 cases per 10,000 patient years. The risk is greatest if you use high doses of simvastatin.

Rhabdomyolysis is a very rare (1 case for every 10 million prescriptions), but serious complication of statin use.

In rhabdomyolysis, myoglobin released from severe muscle breakdown can damage the kidneys.

Rhabdomyolysis risk is increased with several commonly used drugs such as gemfibrizol (Lopid) and erythromycin. Make sure you review potential medication interactions with your physician.

Simvastatin has the greatest risk of medication interaction due to its metabolism pathway.

Pravastatin and rosuvastatin have the lowest risk of muscle related complications.

2)Liver-related side effects

Liver test elevations are typically asymptomatic, reversible, and dose related. The abnormalities are typically seen during the first 12 weeks of treatment.

If your liver tests are only mildly elevated (<2-3x), your physician may decide to continue therapy.

The FDA recently recommended that the recommendation for routine liver function testing be removed.

The incidence of liver failure is the same as the general population.

3)Diabetes

Recently, several studies reported an increased risk of Type 2 diabetes among statin users.

The risk was greatest at the highest medication doses.

The reason for this increased risk is unknown.

Because of these findings, the FDA recently added a warning label to the statins that they can raise sugar and HA1c levels.

There is currently no data to suggest that statins play a significant role in raising your sugar levels if you already have diabetes.

4)Memory changes

This is an area of ongoing investigation, with a history of conflicting studies

Although the diabetes and memory findings are concerning, risk must always be balanced with benefit.

In a person at high risk for CVD, the benefits of statin therapy (reduced frequency of heart attacks and strokes) typically outweigh the risks.

The risk-benefit relationship is important, even if you have diabetes.

Make sure you review this with your physician before making any changes in therapy.

If LDL goals aren’t reached using lifestyle changes and statins, combination therapy with other medications such as niacin, ezetamide and the fibrates are an option.

The decision to begin any medication is a serious one.

Review information that is available so you can make an informed decision.

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