Lipid Disorders

lipid_abnormalities_Secondary_causes_53eLipid Disorders
in: CURRENT Medical Dx & Tx 2014, Fifty-Third Edition > Chapter 28. Lipid Disorders
Robert B. Baron, MD, MS
http://www.accessmedicine.com/content.aspx?aid=16064

The two main lipids in blood are cholesterol and triglyceride. They are carried in lipoproteins

Cholesterol is an essential element of all animal cell membranes and forms the backbone of steroid hormones and bile acids

triglycerides are important in transferring energy from food into cells

Why lipids are deposited into the walls of large and medium-sized arteries—an event with potentially lethal consequences—is not known.

Lipoproteins are usually classified on the basis of density, which is determined by the amounts of triglyceride (which makes them less dense) and apoproteins (which makes them more dense).

The least dense particles, known as chylomicrons, are normally found in the blood only after fat-containing foods have been eaten.

Least dense are the large, very-low-density lipoproteins (VLDL), consisting mainly of triglyceride.

HDL particles … participate in reverse cholesterol transport

The higher the level of low-density lipoproteins (LDL) cholesterol, the greater the risk of atherosclerotic heart disease

the higher the high-density lipoproteins (HDL) cholesterol, the lower the risk of coronary heart disease (CHD)

Middle-aged men whose serum cholesterol levels are in the highest quintile for age (above about 230 mg/dL or 5.95 mmol/L) have a risk of coronary death before age 65 years of about 10%; men in the lowest quintile (below about 170 mg/dL or 4.40 mmol/L) have a 3% risk.

Death from CHD before age 65 years is less common in women, with equivalent risks one-third those of men.

The exact mechanism by which LDL particles result in the formation of atherosclerotic plaques—or the means whereby HDL particles protect against their formation—is not known.

The natural oxidation of LDL particles may be particularly atherogenic. Receptors on the surface of macrophages within atherosclerotic plaques bind and accumulate oxidized LDL. The formation of antibodies to oxidized LDL may also be important in plaque formation.

Familial hypercholesterolemia, rare in the homozygous state (about one per million) is a condition in which the cell-surface receptors for the LDL molecule are absent or defective, resulting in unregulated synthesis of LDL.

familial hyperchylomicronemia

Genome-wide association studies have identified additional genetic variants responsible for differences in serum lipids.

In fasting serum, cholesterol is carried primarily on three different lipoproteins—the VLDL, LDL, and HDL molecules.
Total cholesterol equals the sum of these three components

Two persons with the same total cholesterol of 275 mg/dL (7.11 mmol/L) may have very different lipid profiles … The second would have more than a tenfold higher CHD risk than the first, assuming no differences in other factors.

There is no true “normal” range for serum lipids.
In Western populations, cholesterol values are about 20% higher than in Asian populations and exceed 300 mg/dL (7.76 mmol/L) in nearly 5% of adults. About 10% of adults have LDL cholesterol levels above 200 mg/dL (5.17 mmol/L).
Total and LDL cholesterol levels tend to rise with age in persons who are otherwise in good health.

Therapeutic Effects of Lowering Cholesterol

Diabetes and alcohol use, in particular, are commonly associated with high triglyceride levels

Most patients with high cholesterol levels have no specific symptoms or signs.

  • cardiovascular events
  • cholesterol-lowering therapy
  • heart disease mortality
  • lipid fractions
  • overall risk of developing cardiovascular disease
  • primary prevention: patients without cardiovascular disease
  • secondary prevention: patients with known cardiovascular disease
  • treatment algorithms

Therapeutic Effects of Lowering Cholesterol

Therapeutic Effects of Lowering Cholesterol
in: CURRENT Medical Dx & Tx 2014, Fifty-Third Edition > Chapter 28. Lipid Disorders
Robert B. Baron, MD, MS
http://www.accessmedicine.com/content.aspx?aID=16091

Reducing cholesterol levels in healthy middle-aged men without CHD (primary prevention) reduces their risk in proportion to the reduction in LDL cholesterol and the increase in HDL cholesterol.
Treated adults have statistically significant and clinically important reductions in the rates of myocardial infarctions, new cases of angina, and need for coronary artery bypass procedures.

Rosuvastatin … JUPITER … a combined end point of myocardial infarction, stroke, revascularization, hospitalization for unstable angina, or death from cardiovascular causes in both men and women. The NNT for 1 year to prevent one event was 169.

Primary prevention studies have found a less consistent effect on total mortality.
The JUPITER trial … reduction in death from any cause. The NNT for 1 year was 400.

In patients with CHD, the benefits of cholesterol lowering are clearer.
The NNT to prevent a non-fatal myocardial infarction or a coronary artery disease death in these three studies were between 12 and 34. Aggressive cholesterol lowering with these agents causes regression of atherosclerotic plaques in some patients, reduces the progression of atherosclerosis in saphenous vein grafts, and can slow or reverse carotid artery atherosclerosis.
Meta-analysis suggests that this latter effect results in a significant decrease in strokes.
Results with other classes of medications have been less consistent.
For example, gemfibrozil treatment …

The disparities in results between primary and secondary prevention studies highlight several important points.
The benefits and adverse effects of cholesterol lowering may be specific to each type of drug; the clinician cannot assume that the effects will generalize to other classes of medication.
Second, the net benefits from cholesterol lowering depend on the underlying risk of CHD and of other disease.
In patients with atherosclerosis, morbidity and mortality rates associated with CHD are high, and measures that reduce it are more likely to be beneficial even if they have no effect—or even slightly harmful effects—on other diseases.