​Kembara Xtra - Medicine - Hypertriglyceridemia (HTG)

​Kembara Xtra - Medicine - Hypertriglyceridemia (HTG)
A prevalent kind of dyslipidemia known as hypertriglyceridemia (HTG) is defined by an excessive amount of triglycerides (TGs) in the fasting plasma.
– TGs are large sources of dietary energy and are fatty molecules that naturally occur in vegetable oils and animal fats.
– TGs that have been absorbed are contained in chylomicrons and very low-density lipoproteins (VLDL).
HTG levels below 500 mg/dL, and especially values below 1,000 mg/dL, are risk factors for acute pancreatitis.
– At these TG levels, there is a 10–20% risk.
– Acute pancreatitis' third most common cause
At concentrations below 175 mg/dL, HTG is also independently linked to atherosclerotic cardiovascular disease (ASCVD).
– Persistent HTG is regarded as a risk factor by the American Heart Association (AHA) and the American College of Cardiology (ACC).
– According to a sizable Danish population research published in 2018, people with TG levels below 264 mg/dL had a 10-year risk of major adverse cardiovascular events comparable to that of people who are statin-eligible.
– The cause-and-effect connection between HTG and ASCVD hasn't been conclusively proven, though.
Additionally, there is no evidence that reducing TG lowers cardiovascular risk.
AHA and ACC divide HTG into two groups: - Moderate: 175 to 499 mg/dL (2.0 to 5.6 mmol/L), with excess VLDL being the main factor; - Severe: 500 mg/dL (5.6 mmol/L), with excess VLDL and chylomicrons 

Epidemiology 

Male > female as the predominant gender and Hispanic, white as the predominant race. Prevalence

25–33% of Americans had TG levels below 150 mg/dL.
1.7% have TG values below 500 mg/dL.
Peak prevalence between 50 and 70 years of age 
Familial mixed hyperlipidemia and familial HTG are the two hereditary disorders associated with HTG that afflict less than 1% of the general population each.

Pathophysiology and Etiology 
Factors that include primary, familial, acquired (sporadic), and lifestyle-related
 Overweight and obesity Inactivity Cigarette smoking
Extremely high carbohydrate diets (>60% of total calorie intake) with excessive alcohol consumption - Health problems
 Metabolic syndrome/insulin resistance Type 2 diabetic mellitus
Low thyroid function
Chronic liver disease, nephrotic syndrome, and chronic kidney disease
- Certain drugs - Pregnancy (typically physiologic and transitory); - Autoimmune illnesses (e.g., systemic lupus erythematosus); - Paraproteinemias (e.g., macroglobulinemia, myeloma, lymphoma, lymphocytic leukemia); - Pregnancy
 Atypical antipsychotic medications, such as quetiapine
Oral estrogens, protease inhibitors (such as ritonavir and darunavir), nonselective -blockers, bile acid sequestrants, glucocorticoids, interferon, retinoids, rosiglitazone, tamoxifen and raloxifene, thiazides, and cytophosphamide

Genetics: Autosomal recessive inheritance of lipoprotein lipase impairment causes familial chylomicronemia (type 1 dyslipidemia); incidence in the general population: 0.0001%
Familial mixed hyperlipidemia (type IIb) is typically autosomal dominant and is brought on by excessive apolipoprotein (APO) B-100 production; it has a prevalence of 1%.
Familial dysbetalipoproteinemia (type III) is often autosomal recessive, resulting from the inheritance of two APOE2 mutations, and has a prevalence of 0.01%.
1% frequency of familial HTG (type IV), an autosomal dominant condition brought on by a mutation in the lipoprotein lipase gene.
Type V primary mixed HTG 

Risk factors include genetic predisposition, obesity and being overweight, not exercising enough, type 2 diabetes, alcoholism, and a number of diseases and medications. 

Maintain a healthy body weight, consume dietary fat and refined carbs in moderation, engage in regular cardiovascular exercise, and abstain from drinking excessively.

Accompanying Conditions 
Metabolic syndrome (three of the following): Pancreatitis, coronary artery disease, type 2 diabetes mellitus, and insulin resistance. Dyslipidemias: Low levels of high-density lipoprotein (HDL) cholesterol; high levels of LDL, non-HDL, and total cholesterol; small, dense LDL particles. Low levels of HDL cholesterol (40 mg/dL in men, 50 mg/dL in women) and abdominal obesity (waist circumference >35 inches in women and >40 inches in men). - BP = 130/85 mm Hg
- Nonalcoholic steatohepatitis (NASH), polycystic ovarian syndrome, and fasting blood sugar less than 100 mg/dL 

History-telling Usually asymptomatic
Patients with chylomicronemia syndrome may experience paresthesias, vertigo, headaches, and memory loss.
Pancreatitis causes vomiting, nausea, and epigastric pain.
Check for further cardiac risk factors.
A history of coronary artery disease in the family 

clinical assessment 
Epigastric discomfort in pancreatitis, obesity, overweight (body mass index 25 kg/m2), eruptive cutaneous, tuberous, and striate palmar xanthomas, lipemia retinalis, hepatomegaly in NASH, and chylomicronemia 

distinction between primary and secondary HTG


Initial test results from the laboratory and imaging
The USPSTF advises screening persons aged 40 to 75 years to detect dyslipidemia and determine 10-year ASCVD risk; repeat every 5 years. Serum: turbid with milky supernatant. Fasting (12 hours) or nonfasting lipid profile.
- The American Academy of Pediatrics advises screening for dyslipidemia in all children between the ages of 9 and 11 and 17 and 21, whereas the USPSTF found insufficient support for screening in children and adolescents.
– Regardless of lipid levels, statin medication may be recommended for some persons (e.g., those with clinical ASCVD, diabetes) to reduce their LDL and ASCVD risk.
– Fasting measurement to confirm severe HTG.

Evaluation for secondary causes - Creatinine, urine protein measurement for nephrotic syndrome, renal failure - Glycosylated hemoglobin, fasting or postprandial glucose for type 2 diabetic mellitus - TSH, a hormone used to treat hypothyroidism
- For pregnancy, human chorionic gonadotropin
Atherosclerosis: heart stress testing, coronary CT angiography, cardiac catheterization, and coronary angiography. Pancreatitis: serum lipase; US and/or CT of the pancreas. 

Tests in the Future & Special Considerations

Repeat the lipid panel two months after starting treatment. In individuals whose LDL cannot be measured due to extremely high TGs, high levels of apoB (>130 mg/dL) are a substantial predictor of coronary mortality. However, there is insufficient support for routine clinical apoB testing.

Management 
Unless the patient is at danger for pancreatitis owing to significant HTG (TG 500 mg/dL), reducing cardiovascular risk through lowering LDL should take precedence over lowering TG.

All patients should start with therapeutic lifestyle adjustments, which can cut TG by as much as 50%: Moderate-intensity exercise can lower TG by 20–30%. Dietary modification (by reducing carbohydrate intake to 50% of calories and restricting alcohol intake).
- A 5–10% weight decrease can result in a 20% reduction in TG.
- People with extremely high TG should avoid drinking.
Look for secondary causes that can be fixed, cure the underlying condition, or stop using the offending medication.
If you have diabetes, improve glycemic control.
Manage other cardiac risk factors include smoking, diabetes, and hypertension.
Screen other family members is the primary HTG.

First Line of Medicine
The most efficient medications for lowering cardiovascular risk are statins, which primarily target LDL but may also reduce TG by 15–30% (2).[A]. Although the AHA/ACC algorithm considerably overestimates risk, 2018 ACC/AHA guidelines recommend starting medication for 10-year ASCVD risk 7.5% and other clinical criteria (1)[C]. Dosing is determined by the desired statin intensity based on the risk of ASCVD. Adverse responses include myalgias, myopathy, and rhabdomyolysis (particularly if taken with fibrates); the use of rosuvastatin and atorvastatin during pregnancy and lactation is not recommended.

Fibrates are the most efficient medications for lowering TG by up to 50%; they are mostly used to lower pancreatitis risk in patients with severe HTG, and they have been found to reduce nonfatal myocardial infarction but not all-cause mortality (3).[A]:
30 to 200 mg of fenofibrate per day is preferable.
- Adverse reactions: GI distress, hepatotoxicity, cholelithiasis, myalgias, rhabdomyolysis (when paired with a statin), gemfibrozil-warfarin interaction (increased anticoagulation), gemfibrozil-600 mg BID; avoid in combination with statins due to high risk of muscle injury. Next Line
Omega-3 fatty acids from the sea
Omega-3 ethyl esters (Lovaza, other fish oils): 4 g daily or 2 g BID. Icosapent ethyl (Vascepa): 2 g BID; preferable add-on therapy for HTG in individuals with high ASCVD risk
Could reduce TG by 30–50%

 Limited tolerability due to unfavorable GI effects (up to 15% of patients report diarrhea; other symptoms include nausea, abdominal pain, dysgeusia, eructation, and dyspepsia); Conflicting results data

Referral, familial HTG disorders, and HTG resistant to treatment


Acute coronary syndrome, acute pancreatitis, and admission
The following therapies can be utilized in acute hypertriglyceridemic pancreatitis to quickly and safely decrease TG to 500 mg/dL: - Therapeutic plasma exchange (apheresis) for one to three days - Infusion of insulin
Discharge criteria: stabilization of acute complicating illness. Regular insulin 0.1 to 0.3 U/kg/hr IV for 2 to 4 days. Administer separate infusion of dextrose 5% if blood glucose is below 200 mg/dL.

Follow-up 2 months after the start of the therapy or its change (repeat fasting lipid profile) 
patient observation
Maintain TG between 500 and 1,000 mg/dL to lower the risk of developing acute pancreatitis. Fasting lipid profiles every 6 to 12 months.
Creatine phosphokinase if the patient develops myalgias; Hepatic transaminases 

Diet 
Limit dietary fat to 30% of total calories consumed; if TG is below 1,000 mg/dL, further limit to 15% of total calories consumed.
Limit your consumption of carbs (particularly sweets and simple carbohydrates) to 60% of your total calories.
A low-fat diet decreases TG 10% to 15% less than a Mediterranean-style diet.
Increase omega-3 polyunsaturated fatty acids from marine sources. Consume fatty fish like trout, salmon, mackerel, and sardines.
Trans fatty acids should be eliminated.
Increase your intake of fiber and stay away from refined carbohydrates.
Moderate alcohol consumption (less than 1 oz per day) or total abstinence if TGs are really high.

Modification of Lifestyle 
Quitting smoking can lower your risk of cardiovascular disease.


Patients with primary HTG typically need lifelong treatment. Prognosis: Good with TG level normalization.

complications include pancreatitis, chylomicronemia syndrome, and atherosclerosis.