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Cholesterol

http://clincalc.com/cardiology/ascvd/pooledcohort.aspx

A lipid present in the cell membrane and sub cellular organelles throughout the body tissues.

Maintains membrane fluidity and influences Transmembrane signaling and other essential cellular functions.

Blood levels are maintained by endogenous production and intestinal absorption.

US adults have elevated cholesterol levels compared to evolutionary ancestors.

Brain cholesterol accounts for 25% of stores in the body and promotes myelin formation, synaptogenesis and neuronal plasticity (Valenza).

Cholesterol can be used as is, as a structural component of cellular membranes, or it can be used to synthesize steroid hormones, bile salts, and vitamin D.

A backbone for all steroid hormone production including: cortisol, estrogen, testosterone and aldosterone.

20% of serum cholesterol comes from food.

The body produces about 800 mg of cholesterol per day and about half of that is used for bile acid synthesis producing 400–600 mg daily. 

The risk associated with increasing total cholesterol is continuous and graded, there are no clear threshold values to discriminate subjects who will develop coronary artery disease from those who will not.

Mean age adjusted total cholesterol is 203 mg/dL among adults 20 years or older.

High cholesterol associated with twice the risk of heart disease as people with lower levels.

33.5% Americans have high low-density lipoprotein.

Very low cholesterol levels are associated with violence, and suicide.

Fewer than half adults with high LDL cholesterol get treatment.

In a study of 200,000 peoples lipid profiles studying how the time since last meal affected levels found: HDL and total cholesterol values varied less than 2% with different durations of fasting, triglycerides values varied by 20%, and LDL, had a variation of about 10% (Sidhu D, Naugler C).

Statins, cholesterol absorption inhibitors, and PCSK9 inhibitors lower the plasma cholesterol level by increasing the expression of the LDL receptor on liver cells, stimulating the removal of LDL cholesterol from the blood.

In the secondary analysis of 8270 participants in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm, nonfasting lipid levels were similar to fasting lipid levels measured 4 weeks apart in the same participants in association with incident cardiovascular events overall and by randomized statin therapy.

Concordance of fasting and nonfasting lipid levels for classifying participants into appropriate risk categories was high.

The study provides robust evidence supportive of broader adoption of nonfasting lipid level measurement in clinical practice.

An estimated 105 million American adults have total blood cholesterol 200 mg/d/L or higher and of these 42 million have levels of 240 mg/dL or higher and are at high risk for coronary artery disease.

Average cholesterol levels increase from the second to the sixth decade and then plateau.

High total cholesterol more common among males than females in younger individuals with a reversal of the pattern after the age of 55 years.

Prevalence of cholesterol equal or greater than 200 mg/dL ranges from 29.8% among 20-34 year old women to 84.5% among 65-74 year old women.

Reductions in cholesterol responsible for approximately 33% of the decline in coronary mortality.

Cholesterol lowering with statins proportionally reduces stroke risk.

New guidelines make no recommendations for specific LDL-cholesterol or non-HDL targets for the primary and secondary prevention of atherosclerotic cardiovascular disease.

Thyroid hormone analogue eprotirone utilized in a randomized, placebo controlled, double blind trial in patients with hypercholesterolemia on statins was associated with decreases in serum LDL levels and similar reductions in serm apoliprotein B, triglycerides and Lp(a) lipoprotein (Ladenson PW).

Lowering average cholesterol levels is beneficial in patients with preexisting heart disease regardless of age.

Cholesterol Treatment Trialists’ collaborators observed a 5-6% reduction in vascular events for every 10 mg/dL decrease serum LDL-C levels.

The association between plasma cholesterol and risk of coronary artery disease diminishes with increasing age.

Lifetime risk at age 40 for coronary artery disease through age 80 for men with total cholesterol levels less than 200 mg/dL, 200 to 239 mg/dL, and 240 mg/dL is 31%, 43% and 57% respectively, and for women the lifetime risks are 15%, 26% and 33%.

High density lipoprotein cholesterol levels have a strong inverse relation to incident major cardiac events, even among patients with very low levels of LDL-C with statin therapy

Levels are frequently elevated in pregnancy and should be performed at least 6 weeks postpartum for adequate assessment.

Smith-Lemli-Opitz syndrome associated with decreased synthesis of cholesterol causing multiorgan failure.

Among adults aged 40 years and older, higher serum cholesterol levels were associated with higher risk of POAG, while 5 or more years of statin use compared with never use of statins was associated with a lower risk of POAG.”

The American College of Cardiology (ACC) and the American Heart Association (AHA) recently developed new standards.

The focus of measures are to identify whether someone already has or is at risk for atherosclerotic cardiovascular disease (ASCVD) and could benefit from treatment.

The new practice guidelines outline the most effective treatments that lower blood cholesterol in those individuals most likely to benefit to help reduce future heart attack or stroke risk.

Among US adults, the higher the consumption of dietary cholesterol or eggs is significantly associated with a higher risk of incident CVD and all-cause mortality in a dose response manner (Zhong V).

For primary prevention 2018 guidelines suggest treatment recommendations should be based on a patient’s overall cardiovascular disease risk profile estimated using the 10 year pool cohort equations cardiovascular risk calculator.

Lifetime risk―estimates how likely you are to have a heart attack and stroke during your lifetime are utilized rather than absolute cholesterol levels and include:

Coronary artery calcium score (CAC)―a test that shows the presence of plaque or fatty build-up in the artery walls

High-sensitivity C-Reactive Protein (CRP)―a blood test that measures the amount of CRP, a marker of inflammation, with higher levels have been associated with heart attack and stroke

Ankle brachial index―the ratio of the blood pressure in the ankle compared to blood pressure in the arm, which can predict peripheral artery disease (PAD).

The presence of familial hypercholesterolemia.

 
Individuals aged 70 to 100 years with elevated low-density lipoprotein (LDL) cholesterol have the highest risk for myocardial infarction and atherosclerotic cardiovascular disease (ASCVD).

Lipid-lowering therapies are also effective for reducing cardiovascular events in individuals aged 75 years or older.

 

 

Copenhagen General Population Study (CGPS) analyzed 91,131 individuals over 

 

7.7-year follow-up period.

 

 

Myocardial infarction per 1.0 mmol/L increase in LDL cholesterol increased with a hazard ratio of 1.34, and for ASCVD per 1.0 mmol/L increase in LDL cholesterol, with a hazard ratio of 1.16. 

 

 

The risk was high in all age groups, but especially among those aged 70 to 100 years.

 

 

Risk of myocardial infarction was also increased with a 5.0 mmol/L or higher LDL cholesterol versus less than 3.0 mmol/L in individuals aged 80-100 years.

 

Management includes: Adopting a heart-healthy lifestyle.

Eating a diet rich in vegetables, fruits, and whole grains; this also includes low-fat dairy products, poultry, fish, legumes, and nuts.

Eating a diet that limits intake of sweets, sugar-sweetened beverages and red meats.

Getting regular exercise.

Maintaining a healthy weight.

Not smoking.

Taking statins may be necessary:

In the presence of ASCVD statin therapy is the most effective and safest way to lower cholesterol and the chances of having a heart attack or stroke.

Very high LDL cholesterol , 190 mg/dL or higher

For Type 2 diabetics between 40 and 75 years of age.

For individuals with likelihood of having a heart attack or stroke in the next 10 years of 7.5% or higher. and are between 40 and 75 years of age.

For patients whose 10 year risk of ASCVD is 20% or more should try to reduce LDL-C levels by at least 50%, the same goal as for people with clinical ASCVD.

For patients with a family history of premature heart attack or stroke.

LDL-cholesterol > 160 md/dL

hs-CRP >2

Results from other special testing such as CAC scoring, ABI.

People who have had a heart attack, stroke or other types of ASCVD tend to benefit the most from taking the highest dose of statin therapy.

For patients with very high risk ACVD the secondary goal is to reduce LDL-cholesterol to less than 70 mg/dL: if this cannot be done with the maximum tolerated statin therapy, guideline recommends ezetimibe and if needed a PCSK9 inhibitor.

Because not all patients will be able to take the optimum dose of statin, non-statin drugs may be recommended:

Have side effects from statins

Cannot tolerate the ideal dose

Take other drugs that interact with a statin including:

Bile acid sequestrants

Niacin

Ezetemibe

Fibrates

For most people, dietary cholesterol has only a modest effect on the amount of cholesterol in the bloodstream.

Guidelines for Americans eliminated an earlier recommendation to limit dietary cholesterol to 300 milligrams (mg) per day.

Saturated fat in the diet clearly does raise LDL by a significant amount and should still be consumed in limited quantities.

Foods high in fiber, low in saturated fat can lower cholesterol.

The best diet to lower cholesterol is rich in fruits, vegetables, fish, and whole grains.

The more of these healthful foods eaten, the less one consumes foods that are high in saturated fat and highly refined carbohydrates, which both damage the cardiovascular system.

High-fiber foods help reduce your cholesterol level by making unhealthy dietary fats harder to absorb from the gut.

Inclisiran is a small-interfering RN agent which blocks PCSK9 protein production in the liver through RNA interference, which in turn decreases LDL-C levels in the blood.

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