Hyperlipidemia


Introduction[edit | edit source]

Stop! do you know your cholesterol number (6944338085).jpg

Hyperlipidemia is a medical term for abnormally high levels of fats (lipids) in the blood (commonly known as high cholesterol). The two major types of lipids found in the blood are triglycerides and cholesterol. Although hyperlipidemia can be inherited, it’s more often the result of unhealthy lifestyle choices.

  • Triglycerides are made when your body stores the extra calories it doesn’t need for energy. They also come directly from your diet in foods eg red meat and whole-fat dairy. A diet high in refined sugar, fructose, and alcohol raises triglycerides.
  • Cholesterol is produced naturally in your liver and every cell in your body uses it. Similar to triglycerides, cholesterol is also found in fatty foods like eggs, red meat, and cheese.

Raised cholesterol increases the risks of heart disease and stroke.

  • Globally, a third of ischaemic heart disease is attributable to high cholesterol.
  • Overall, raised cholesterol is estimated to cause 2.6 million deaths (4.5% of total) and 29.7 million disability adjusted life years (DALYS), or 2.0% of total DALYS.
  • Raised total cholesterol is a major cause of disease burden in both the developed and developing world as a risk factor for Ischemic heart disease and stroke.[1]

Clinically Relevant Anatomy[edit | edit source]

Cholesterolfunction.jpg

Cholesterol is a lipophilic molecule that is essential for human life. It has many roles that contribute to normally functioning cells. For example cholesterol is an

  • Important component of the cell membrane
  • Contributes to the structural makeup of the membrane as well as modulates its fluidity
  • Functions as a precursor molecule in the synthesis of vitamin D, steroid hormones (e.g., cortisol and aldosterone and adrenal androgens), and sex hormones (e.g., testosterone, estrogens, and progesterone).
  • Is a constituent of bile salt, which is used in digestion to facilitate absorption of fat-soluble vitamins A, D, E, and K.

Since cholesterol is mostly lipophilic, it is transported through the blood, along with triglycerides, inside lipoprotein particles (HDL, IDL, LDL, VLDL, and chylomicrons).

Cholesterol can be introduced into the blood through the digestion of dietary fat via chylomicrons. However, since cholesterol has an important role in cellular function, it can also be directly synthesized by each cell in the body. The synthesis of cholesterol begins from Acetyl-CoA and follows a series of complex reactions primarily in the liver, which accounts for most de-novo cholesterol synthesis.[2]

Reverse Cholesterol Transport[edit | edit source]

Reverse cholesterol transport is a mechanism by high-density lipoprotein that works as the atheroprotective effect, means protects from atherosclerosis formation.[3]

Mechanism of Injury / Pathological Process[edit | edit source]

Peripheral Arterial Disease.gif

If there is excessive cholesterol in the blood circulation, some of the excesses can become trapped in arterial walls, over time, this builds up and forms plaques. These plaques can narrow blood vessels and make them less flexible; this process is called atherosclerosis.

  • Atherosclerosis of the coronary circulation results in coronary arterial disease (CAD)
  • Atherosclerosis of the carotid and vertebral arteries results in stroke manifestations.

CAD (causing ischemic heart disease) is the leading cause of death worldwide, followed by stroke-related deaths. Together these pathologies remained as the leading causes of death globally in the last 15 years, accounting for 15.2 million deaths in 2016. 

Trans fats have adverse effects on lipid and lipoprotein metabolism and promote endothelial dysfunction, insulin resistance, inflammation, and arrhythmias.[4]

Depiction of a person suffering from high cholesterol.png

Familial combined hyperlipidemia[edit | edit source]

Familial combined hyperlipidemia (FCH), also known as mixed hyperlipidemia, is the genetic form of hyperlipidemia and one of the most common genetic lipid disorders. It's a polygenic in nature[5] , means genetic effects that arise from the interaction of multiple genes.

Its prevalence is approximately 0.5 to 4% . It's also found that 10% to 20% of individuals with premature myocardial infarction are found to have familial combined hyperlipidemia.[6]

Clinical Presentation[edit | edit source]

Hyperlipidemia has no symptoms, so the only way to detect it for a doctor to perform a blood test ie a lipid panel or a lipid profile. This test determines cholesterol levels.

History and Examination[edit | edit source]

When a diagnosis of hyper lipidemia is found the following are recommended, both history and physical examination can yield useful information.

  • If there is a positive family history of premature atherosclerotic cardiovascular disease, constructing a family tree is useful.
  • Ask about secondary causes such as smoking, diabetes, dietary intake of total calories, saturated, and trans fats, physical activity and drug therapies
  • Ask about symptoms of CV disease (angina pectoris, intermittent claudication, transient ischemic attacks) is also important.
  • In patients with hypercholesterolemia, palpitate all pulses and elicit carotids and femoral bruits.
  • In suspected familial hypercholesterolemia patients, a careful examination of the heart for supra-valvar aortic stenosis due to atheroma deposition is warranted.[7]

Diagnostic Procedures[edit | edit source]

A plasma lipid profile should be measured in all adults older than 40 years, preferably after a 10 to 12-hour overnight fast. The lipid profile reports levels of:

  • total cholesterol
  • low-density lipoprotein (LDL) cholesterol
  • high-density lipoprotein (HDL) cholesterol
  • triglycerides

Screening recommendations:

Raised cholesterol Situation and trends[edit | edit source]

  • Raised cholesterol increases the risks of heart disease and stroke.
  • Globally, a third of ischaemic heart disease is attributable to high cholesterol.
  • Overall, raised cholesterol is estimated to cause 2.6 million deaths (4.5% of total) and 29.7 million disability adjusted life years (DALYS), or 2.0% of total DALYS.
  • Raised total cholesterol is a major cause of disease burden in both the developed and developing world as a risk factor for Ischemic heart disease and stroke.
  • In 2008 the global prevalence of raised total cholesterol among adults (≥ 5.0 mmol/l) was 39% (37% for males and 40% for females). Globally, mean total cholesterol changed little between 1980 and 2008, falling by less than 0.1 mmol/L per decade in men and women.
  • The prevalence of elevated total cholesterol was highest in the WHO Region of Europe (54% for both sexes), followed by the WHO Region of the Americas (48% for both sexes). The WHO African Region and the WHO South East Asian Region showed the lowest percentages (22.6% for AFR and 29.0% for SEAR).
  • The prevalence of raised total cholesterol increased noticeably according to the income level of the country. In low income countries around a quarter of adults had raised total cholesterol, in lower middle income countries this rose to around a third of the population for both sexes. In high-income countries, over 50% of adults had raised total cholesterol; more than double the level of the low-income countries.[1]

Management / Interventions[edit | edit source]

Heart food.jpg

The cornerstones of treatment of hypercholesterolemia are

  • a healthy lifestyle,
  • an optimum weight,
  • no smoking,
  • exercising for 150 minutes per week, and
  • a diet low in saturated and trans-fatty acids and enriched in fiber, fruit, and vegetables and fatty fish. [7]

If lifestyle changes aren’t enough to treat hyperlipidemia, medication will be inititiated. Common cholesterol- and triglyceride-lowering medications include:

  • statins, such as:
    • atorvastatin (Lipitor)
    • fluvastatin (Lescol XL)
    • lovastatin (Altoprev)
    • pitavastatin (Livalo)
    • pravastatin (Pravachol)
    • rosuvastatin (Crestor)
    • simvastatin (Zocor)
  • bile-acid-binding resins, such as:
    • cholestyramine (Prevalite)
    • colesevelam (WelChol)
    • colestipol (Colestid)
  • cholesterol absorption inhibitors, such asezetimibe (Zetia)
  • injectable medications, such as alirocumab(Praluent) or evolocumab (Repatha)
  • fibrates, like fenofibrate (Fenoglide, Tricor, Triglide) or gemfibrozil (Lopid)
  • niacin (Niacor)
  • omega-3 fatty acid supplements
  • other cholesterol-lowing supplements[8]

Prognosis[edit | edit source]

The biggest risk of hypercholesterolemia is adverse cardiac events. However, since the introduction of the statins, the mortality associated with hypercholesterolemia has significantly decreased in many trials. Today, cholesterol-lowering is a useful strategy for the primary prevention of heart disease.

Complications[edit | edit source]

  • Heart Disease
  • Stroke
  • Peripheral vascular disease

Physiotherapy[edit | edit source]

Exercise photo.jpg

Hypercholesterolemia is common and associated with enormous morbidity and mortality, leading to high healthcare costs. To manage the condition, an interprofessional team dedicated to the prevention of heart disease is essential. Besides physicians, the role of the pharmacist, nurse, dietitian, and physical therapist are critical in the management of hypercholesterolemia.

Physiotherapy Effects of exercise on lipid profiles (to help guide your choice of exercise)

  • While may not lower LCL-C aerobic exercise may improve insulin sensitivity, lower triglyceride levels and increase HDL
  • Regular physical activity has been shown to increase HDL cholesterol while maintaining, and theoretically offsetting increases in, LDL cholesterol and triglycerides. There appears to be a linear dose–response relationship between activity levels and HDL cholesterol levels.
  • More intense activity, however, is required to elicit reductions in LDL cholesterol and triglyceride levels.
  • Prolonged moderate-intensity aerobic exercise should be recommended as a starting point for those who have previously been sedentary or are new to exercise.
  • Aerobic exercise at high intensities appears to be effective in improving the lipid profile.
  • Gym equipment.png
    Increases in calorific expenditure associated with aerobic exercise (via increased intensity and/or duration) have been shown to positively influence lipoprotein lipase activity, HDL cholesterol levels and the lipid profile.
  • During resistance training, it has been shown consistently that the increased volume of movement (via increased numbers of sets and/or repetitions) has a greater impact upon the lipid profile than increased intensity (e.g. via high-weight low-repetition training).
  • Resistance training presents a viable alternative to aerobic exercise or is an effective intervention independently.
  • High-intensity exercise (>85 % 1 RM) has been shown to be no more effective than moderate-intensity exercise (50–85 % 1 RM).
  • The addition of resistance training to aerobic exercise will supplement—and possibly enhance—the effects on the lipid profile,[9]

A pilot trial found that ferritin in postmenopausal women participating in Resisted Training (RT) over 15 weeks positively correlated with ferritin, total cholesterol, low-density lipoprotein, and non-high-density lipoprotein cholesterol while negatively correlated with HDL. However, a large-scale cohort is needed to confirm these findings[10].

Further Information[edit | edit source]

You can check our great pages on the other lipid disorders;

References[edit | edit source]

  1. 1.0 1.1 WHO Raised cholesterol Available from:https://www.who.int/gho/ncd/risk_factors/cholesterol_text/en/ (last accessed 9.3.2020)
  2. Huff T, Jialal I. Physiology, cholesterol.2019 Available from:https://www.ncbi.nlm.nih.gov/books/NBK470561/ (last accessed 9.3.2020)
  3. Poznyak AV, Kashirskikh DA, Sukhorukov VN, Kalmykov V, Omelchenko AV, Orekhov AN. Cholesterol transport dysfunction and its involvement in atherogenesis. International Journal of Molecular Sciences. 2022 Jan 25;23(3):1332.
  4. Janapala US, Reddivari AK. Low Cholesterol Diet. InStatPearls [Internet] 2019 Nov 25. StatPearls Publishing. Available from:https://www.ncbi.nlm.nih.gov/books/NBK551722/ (last accessed 9.3.2020)
  5. Gill PK, Hegele RA. Familial combined hyperlipidemia is a polygenic trait. Current Opinion in Lipidology. 2022 Apr 1;33(2):126-32. BibTeXEndNoteRefManRefWorks
  6. Padda IS, Fabian D, Johal GS. Familial Combined Hyperlipidemia. InStatPearls [Internet] 2023 May 19. StatPearls Publishing. BibTeXEndNoteRefManRefWorks
  7. 7.0 7.1 7.2 Ibrahim MA, Jialal I. Hypercholesterolemia. InStatPearls [Internet] 2019 Feb 16. StatPearls Publishing.Available from:https://www.ncbi.nlm.nih.gov/books/NBK459188/ (last accessed 9.3.2020)
  8. Healthline What You Should Know About Hyperlipidemia Available from:https://www.healthline.com/health/hyperlipidemia (last accessed 9.3.2020)
  9. Mann S, Beedie C, Jimenez A. Differential effects of aerobic exercise, resistance training and combined exercise modalities on cholesterol and the lipid profile: review, synthesis and recommendations. Sports Medicine. 2014 Feb 1;44(2):211-21. Available from:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906547/ (last accessed 9.3.2020)
  10. Ward LJ, Hammar M, Lindh-Åstrand L, Berin E, Lindblom H, Rubér M, Holm AC, Li W. Does resistance training have an effect on levels of ferritin and atherogenic lipids in postmenopausal women?–A pilot trial. Scientific reports. 2020 Mar 2;10(1):1-8.