​Kembara Xtra - Medicine - Hypercholesterolemia

​Kembara Xtra - Medicine - Hypercholesterolemia 
Elevated cholesterol is a substantial risk factor for atherosclerotic cardiovascular disease (ASCVD), according to the basic description.

Subtypes of lipoprotein
- Low-density lipoproteins (LDL): the main therapeutic target
- Atheroprotective effects of high-density lipoproteins (HDL)
TG: Triglycerides

Cardiovascular (CV) system is/are impaired.

Epidemiology 
Hypercholesterolemia affects 7% of children and adolescents in the United States between the ages of 6 and 19 and 28% of Americans over the age of 20.
Prevalence
As people age, disease incidence and prevalence rise.

Pathophysiology and Etiology 
The pathophysiology
- When cholesterol builds up in vascular walls, fatty streaks develop into fibrous plaques.
– Plaque rupture is a result of plaque instability brought on by inflammation.
– The pathogenesis of atherosclerosis, inflammation, and vascular reactivity is multifaceted.
Hypercholesterolemia's etiology
Obesity, diet, excessive alcohol consumption, hypothyroidism, diabetes, inflammatory disease, liver disease, nephrotic syndrome, chronic renal failure, and medications (thiazide diuretics, carbamazepine, cyclosporine, progestins, anabolic steroids, corticosteroids, protease inhibitors, antipsychotics, isotretinoin) are secondary causes. The primary cause is genetic (familial dyslipid

Genetics Familial hypercholesterolemia (FH) - Elevated LDL levels since birth - Heterozygous FH prevalence is 1:300 globally.
- High risk of coronary heart disease at younger ages and a propensity for atherosclerotic disease in early adulthood. Homozygous FH patients often pass away before the age of 20. - Early lipid-lowering medication therapy has been demonstrated to minimize the risk of ASCVD.
It is advised that first-degree relatives get early lipid screening.

Risk Elements 

Obesity, physical inactivity, family history, smoking cigarettes, and binge drinking are all risk factors. Saturated dietary fat has a complicated link with hypercholesterolemia and coronary artery disease.

Preventive measures, regular exercise, weight management, and a diet low in saturated fats (grade 1B)


Accompanying Conditions 
Obesity, high blood pressure, and diabetes mellitus (DM)


DIAGNOSIS
U.S. Preventive Services Task Force (USPSTF) screening recommendations: total cholesterol and HDL cholesterol (HDL-C) every five years for men and women under 40; neither a recommendation for nor a recommendation against screening for adults aged 21 to 39; neither a recommendation for nor a recommendation against screening for children and adolescents.

American diabetic Association: diabetic patients should get yearly dyslipidemia screenings

Child Safety Considerations
The National Heart, Lung, and Blood Institute recommends that all children between the ages of 9 and 11 and between the ages of 17 and 21 get a comprehensive lipid screening. The American Academy of Pediatrics gave their approval to this.
Children who have a family history of familial hypercholesterolemia or early coronary artery disease should be screened.

Review potential secondary etiologies; evaluate other ASCVD risk factors; present history.

clinical assessment 

Non-specific findings; possible BMI calculation and xanthoma examination

Laboratory Results 

Initial examinations (lab, imaging)

Lipid panel (preferably not fasted). LDL is often computed and reliable if TG is less than 350 mg/dL.
If you have hypertriglyceridemia (TG > 440 mg/dL) or a condition that can elevate TG, including pancreatitis, perform fasting blood tests.

In cases of extremely high LDL (>190 mg/dL) or TG (>500 mg/dL), consider the genetic explanation.

Administration Caution 
Multiple rules are in place. LDL target targets are once again emphasized in the 2018 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines. Patients with existing CV disease should be regarded as high risk (secondary prevention), hence risk stratification should only be used for primary prevention.
U.S.: ACC/AHA cholesterol recommendations (2)
– The ACC/AHA states that four groups gain from statin therapy:
Initial LDL-C rise >190 mg/dL: high-intensity statin
Patients 40 to 75 years old with diabetes and LDL-C >70 mg/dL should take a moderate-intensity statin.
Based on pooled cohort equations, ASCVD risk: Visit the calculator at http://tools.acc.org/ASCVD-Risk-Estimator (comment on calculator below).
10-year ASCVD risk is 5% with a Mediterranean diet and regular exercise.
10-year ASCVD risk 7.5-20%: moderate-intensity statin, discuss with patient; 10-year ASCVD risk 5-7.5%: moderate-intensity statin; 30- to 49%-lower LDL-C target; 10-year ASCVD risk 7.5-20%: moderate-intensity statin
High-intensity statin with a target to lower LDL-C by >50% for patients with 10-year ASCVD risk >20%
Secondary ASCVD prevention: high-intensity statins with an aim to lower LDL-C by more than 50%. In very high-risk ASCVD patients, add ezetimibe if LDL levels are greater than 70 mg/dL following maximal statin therapy.
Age >75 years: as tolerated, moderate- or high-intensity statin therapyVery high-risk ASCVD is defined as having numerous high-risk conditions as well as at least one significant ASCVD event:
Important ASCVD occurrences
Ischemic stroke history, symptomatic peripheral arterial disease, acute coronary syndrome, or previous myocardial infarction
Age over 65, heterozygous FH, a history of CABG or PCI, diabetes mellitus, high blood pressure, chronic renal disease, current smoking, a history of congestive heart failure, and LDL-C >100 mg/dL while receiving the best medical care are all high-risk factors.
 The threshold calculated risk at which to treat patients is a matter of debate: The 10-year ASCVD risk estimated by the pooled cohort equations is greatly inflated (by at least 50%). Therefore, go over the advantages and disadvantages of statin therapy with your patients. Consider the patient's age.
United States: USPSTF advice on statin use Adults between the ages of 40 and 75 who do not smoke, have dyslipidemia, hypertension, diabetes, or diabetes with a projected 10-year CVD event risk of 10% or higher: statins with a low to moderate dose (grade B recommended)
- People aged 40 to 75 who have no prior history of cardiovascular disease, at least one CVD risk factor, and an estimated 10-year CVD event risk of 7.5–10%: Low- to moderate-dose statins are advised (grade C).
- Adults 76 years and older without a history of CVD: insufficient data to recommend.
Guidelines for lowering cholesterol from the National Institute for Health and Care Excellence (NICE), United KingdomNICE advises individuals under primary prevention consideration to make lifestyle changes before beginning any statin therapy. The 10-year risk can be assessed using QRISK2 at https:// qrisk.org/three/.
- Start taking atorvastatin 20 mg if your 10-year risk of cardiovascular disease is greater than 10% and you have no history of the disease.
- If there is a known CVD and a 10-year risk of CVD is greater than 10%, begin taking 80 mg of atorvastatin.
Consider taking atorvastatin 20 mg if you're under 85 years old to lower your risk of suffering a nonfatal myocardial infarction, while there is some debate over its efficacy.
– Start atorvastatin 20 mg if estimated glomerular rate is less than 60 or if you have type I diabetes.
ALERT
To prevent acute pancreatitis in hypertriglyceridemia with TG>500 mg/dL, TG reduction becomes the main objective until 500 mg/dL. Unless TGs continue >500, statin medication is typically advised as a first line of treatment. Fibrates may be taken with statins with caution due to an increased risk of rhabdomyolysis.


Prior to starting drug therapy, cornerstone therapies including medication and therapeutic lifestyle changes should be tried.
The majority of persons over 75 years old do not benefit from starting statin medication for primary prevention, according to the available data (ALLHAT-LLT).
4–12 weeks after starting a drug, check the lipid panel to assess response and/or adherence.
- Unless there is a concern about the patient's adherence, subsequent monitoring is generally not recommended.

Statins, the first-line HMG-CoA reductase inhibitors

 Sorted according to intensity
- High intensity (reduces LDL-C by >50%): atorvastatin 40 to 80 mg/day, rosuvastatin 20 to 40 mg/day; - Moderate intensity (reduces LDL-C by 30-49%): atorvastatin 10 to 20 mg/day, rosuvastatin 5 to 10 mg/day; - Low intensity (reduces LDL-C by 30%): simvastatin 20 to 40 mg/

Pregnancy, lactation, or active liver disease are contraindications.

Adverse effects: Mild myalgia is frequently experienced.
- Elevated liver transaminases: alanine aminotransferase (ALT) is measured before to medication to establish baseline; if ALT is greater than three times the upper limit of normal, do not start a statin; routine monitoring is not advised.
- Association with an increase in diabetes cases: 0.1 extra cases per 100 people taking a moderate-intensity statin and 0.3 extra cases per 100 people taking a high-intensity statin.
- Myopathies (quite uncommon but poorly understood)
- Intolerance to statins
Think about switching statins.
Reduced dosage
The majority of patients who have previously stopped taking statins because of side effects are able to resume taking the same or a different statin and tolerate it.
ALERT
Warning from the U.S. Food and Drug Administration: Due to an elevated risk of myopathy, simvastatin at 80 mg/day should not be prescribed.
If there are no symptoms of myopathy, patients who have been taking this medication for more than a year can continue.
 The following dosage limitations are used to lower the risk of myopathy:
Simvastatin 10 mg/day with amiodarone, verapamil, and diltiazem is the upper limit; simvastatin 20 mg/day with amlodipine and ranolazine is the upper limit.

Some HMG-CoA reductase inhibitors may interact negatively with hepatitis C antiviral drugs.
Visit https:// www.hepdruginteractions.org/checker to verify interactions.
When using statins, stay away from grapefruit juice as it may raise the risk of statin myopathy.


pregnant women's issues
Statins are not recommended during pregnancy, and lactation may be risky.

Next Line
If LDL-C is >70 mg/dL on maximum statin therapy, second-line medications are now advised for primary prevention.
Ezetimibe - Can be used alone or in combination with a statin; monotherapy (10 mg/day) or ezetimibe/simvastatin - Effect: lowers LDL-C; one randomized controlled trial shows combination therapy with statin has modest benefits in lowering CV events and CV-related mortality following acute coronary syndromes.
Fibrates, of which the most effective are gemfibrozil and fenofibrate, have a moderate impact on lowering LDL and a strong positive impact on raising HDL. Most patients in more recent research do not have a mortality benefit.
Niacin improves HDL but there is no proof that it leads to better results; it shouldn't be used frequently.
PCSK9 inhibitors, such as monoclonal antibodies alirocumab and evolocumab. The latest research suggests secondary prevention reduces CVD incidence without impacting all-cause death incidence, however it is very expensive.


Healthcare Alternatives 
Omega-3 fatty acids with use of fish oil
Flaxseed, canola oil, soybean oil, almonds, and fatty fish are the sources of this compound. Its effect is to lower TG and LDL levels while raising HDL.
Mortality reduction and overall CV benefit are questionable.

Admission

Recommend rechecking a fasting lipid panel 4–12 weeks after discharge if lipid panel was tested while patient due to myocardial infarction as the initial lab may not have been as accurate.

Take Action 

150 minutes a week of moderate-intensity exercise raises HDL, reduces TC, and aids in weight management.
patient observation
If the first ALT is within the normal range, routine monitoring of liver function tests is no longer advised.
DIET The risk of CV disease is decreased by plant-based diets and the Mediterranean diet, which are high in legumes, fruits, vegetables, nuts, fish, and olive oil.

Complications 

Peripheral artery disease, a myocardial infarction, and a cerebrovascular event

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