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Triglyceride

Triglycerides, as major components of very-low-density lipoprotein (VLDL) and chylomicrons, play an important role in metabolism as energy sources and transporters of dietary fat. 

Elevations in women are more significant than in men as a cause of atherosclerosis.

Levels less than 150 mg/dL are optimal and treatment for levels of 200 mg/dL are recommended.

Level of triglycerides vary depending on length of fasting.

There is a strong inverse relationship between triglyceride level and HDL-cholesterol level.

High triglyceride levels increase the quantity of small, dense LDL particles.

Triglyceride levels:

(mg/dL) (mmol/L)

< 150 < 1.70 Normal range – low risk

150–199 1.70–2.25 Slightly above normal

200–499 2.26–5.65 Some risk

500 or higher > 5.65 Very high – high risk

These levels are tested after fasting 8 to 12 hours. 

Triglyceride levels remain temporarily higher for a period after eating.

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).

A significant independent risk factor for coronary heart disease.

There is a strong association between elevated levels and coronary heart disease.

Adults with elevated triglyceride levels have higher coronary heart disease risk, yet it is unclear whether triglycerides alone caused coronary heart disease or whether they are a surrogate for other concomitant metabolic derangements such as obesity, diabetes, or other lipoprotein elements that confer actual risk.

Triglycerides do not accumulate with the atherosclerotic disease plaque to any significant degree.

TG‘s are mostly found in chylomicrons, which transport dietary fatty acids and cholesterol from the intestine and very low density lipoprotein particles, which transport TG’s from the liver.

Triglycerides up to 500 mg/dL or carried by VLDL which entails a mild to modern risk or increase atherogenocity and risk for an acute cardiovascular event.

At levels above 500 mg per/dL, triglycerides are carried by chylomicrons, which exponentially increased the risk for pancreatitis.

Both triglycerides and cholesterol are carried in plasma by apolipoprotein B (ApoB) containing lipoprotein particles.

Serum TG measurements assess the total mass of TG‘s, not the number or type of particles carrying those TGs.

When TG levels are elevated due to isolate the elevations in chylomicrons, which are too large to enter the arterial wall, atherosclerotic risk is not increased.

Beyond chylomicrons, measured TG levels can also be elevated with either an increase in the TG content of VLDL particles or an increase in the total number of VLDL particles.

Hyperypertriglyceridemia is not a single disease but rather a heterogeneous collection of disorders, with potentially different degrees of cardiovascular risk.

As Triglyceride: HDL cholesterol ratio increases, vascular risk increases.

The link between high triglycerides and atherosclerotic disease relates to LDL-C levels being high enough or HDL-C levels low enough, then the ratio between LDL-C and HDL-C being abnormal that leads to atherosclerotic disease

Data from a national study, collected from 1999 through 2004 revealed that 33% of adults have triglyceride concentrations of greater than 150 mg/deciliter or higher at 18% have concentrations of 200 mg/deciliter or higher.

Several large randomized controlled studies found that diet supplementation with niacin and fibrates do not improve outcomes.

Niacin effectively lowers triglyceride levels but does not lower the risk of coronary heart disease and increases the incidence of infection, bleeding and diabetes.

Large percentages of patients with hypertriglyceridemia are overweight, smoke, and are sedentary.

Only 1.3% of adults report being treated with niacin, fenofibrate, or gemfibrozil.

Fibrates lower TG levels but do not significantly lower coronary heart disease events and actually can increase serious adverse effects when combined with statins.

Among patients with type two diabetes, mild to moderate hyper triglyceridemia and a low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received permafibrate then among those who received placebo,: although the drug lowered triglyceride, VLDL cholesterol, and apo-lipoprotein C- III levels (PROMINENT investigators).

Statin treated patients with triglyceride levels of 150 mg/dL or greater have worse cardiovascular health outcomes than those with well-managed triglycerides of less than 150 mg/dL and HDL-C of greater than 40 mg/dL.

Hypertriglyceridemia is an important cause of acute and recurrent pancreatitis in patients with familial lipid metabolic disorders, diabetic ketoacidosis, excessive alcohol use, hypothyroidism, hormone supplementation, medication use, and pregnancy.

Hypertriglyceridemia causes 1-4% of cases of acute pancreatitis.

Serum triglyceride levels greater than 1000 mg/dL are necessary to diagnose hypertriglyceridemia-induced acute pancreatitis.

TG’s are mostly found in chylomicrons, which transports dietary fatty acids and cholesterol from the intestine and very low density lipoprotein particles, which transport TG’s from the liver.

Dyslipidemia and cardiovascular disease are common in shift workers and eating at night may contribute to this pathophysiology.

 

When individuals eat at night, levels of TG are  similar to eating during the day, however, these levels at night were reached with consuming approximately half the calories. 

 

Dyslipidemia and cardiovascular disease are common in shift workers and eating at night may contribute to this pathophysiology: postprandial lipid metabolism, which leads to hypersensitivity in triglycerides responses when eating at night.

 

24-hour levels of TG were 10% higher when meals were consumed hourly across 24 hours compared to consuming a typical 3-meal schedule while awake during the day and sleeping at night. 

 

Endogenous circadian rhythms of TG, peak at night, were shifted earlier by ~10 hours under baseline conditions whereas the rhythms in total cholesterol, HDL-C or LDL-C remained unchanged and peaked in the afternoon.

 

The time-of-day dependency on postprandial lipid metabolism, which leads to hypersensitivity in TG responses when eating at night, may underlie the dyslipidemia and elevated cardiovascular disease risk observed in shift workers.

Elevated triglyceride management includes:

Weight loss, dietary modification, moderate exercise as first-line lifestyle modification treatments.

For hypertriglyceridemia, restriction of carbohydrates, specifically fructose and fat in the diet and the consumption of omega-3 fatty acids from algae, nuts, fish and seeds are recommended.

Icosapent ethyl (Vascepa)is a highly purified and stable eicosapentaenoic acid (EPA) ethyl ester that lowers triglyceride levels and is used in adjunct to diet in adult patients with triglyceride levels of at least 500 mg/dL.

In the REDUCE-IT trial the risk of primary endpoint of cardiovascular death, nonfatal myocardial infarction, non-fatal stroke, coronary revascularization, or unstable angina was significantly lower by 25% among patients who receive 2 g of Icosapent ethyl twice daily and among those who receive placebo, corresponding to an absolute difference of 4.8 percentage points in the rate of endpoint.

 

The number number of people needed to treat, to prevent one cardiovascular death over five years is 111.

 

Fibrates, omega-3 fatty acids, or niacin should be considered for patients with severely elevated triglyceride levels to reduce the risk of pancreatitis.

 

With acute pancreatitis associated with hypertriglyceridemia, insulin infusion and plasmapheresis should be considered if triglyceride levels remain at 1,000 mg per dL or higher despite conservative management of acute pancreatitis.

 

Elevated triglyceride levels of 150 to 499 mg per dL are associated with increased risk of cardiovascular disease (CVD), and severely elevated levels of 500 mg per dL or higher are associated with increased risk of pancreatitis. 

 

Systematic reviews do not support use of omega-3 fatty acids for the primary prevention of cardiovascular disease.

 

For patients with established cardiovascular disease and elevated triglyceride levels who are already on statins, icosapent (Vascepa) reduces cardiovascular mortality.

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