Lipids, such as cholesterol or triglycerides, are absorbed from the intestines and are carried throughout the body via lipoproteins for energy, steroid production, or bile acid formation. Major contributors to these pathways are cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, and high-density lipoprotein (HDL). An imbalance of any of these factors, either from organic or nonorganic causes, can lead to dyslipidemia.
Several health behaviors can have effects and increase lipid levels. Examples include tobacco use, physical inactivity, nutrition, and obesity. Specifically, nutrition risk factors include the insufficient consumption of fruits, nuts/seeds, vegetables, or high consumption of saturated fats.
Dyslipidemia can be due to familial disorders as well. Autosomal dominant mutations cause most cases of familial hypercholesterolemia in LDL receptors, which causes an elevation in LDL-C levels. Other mutations in the cholesterol pathway have been identified but are less common.
The prevalence of dyslipidemia increases with age. In 2005-2008 an estimated 33.5% of U.S. adults older than 20 years of age had high LDL-C levels. Of these individuals with elevated LDL-C levels, only 48.1% received treatment, and 33.2% had their LDL-C controlled. The prevalence of LDL-C control seemed to be the lowest amongst individuals that were uninsured, Mexican American, or having income below the poverty level.
History is essential in identifying high-risk individuals. Most importantly, social history would include tobacco use or specific details about diet. Past medical history is vital in identifying patients who will need primary prevention versus secondary prevention if statin therapy requires initiation. Lastly, family history is important to identify familial hypercholesterolemia.
The physical exam is limited in dyslipidemia disorders. Xanthomas are deposits of lipids on the skin and sometimes subcutaneous tissue. They are yellowish and can form into plaques, nodules, or plaques. They can present on the palmar crease, which suggests familial dysbetalipoproteinemia, eyelids, or tendons. They typically are associated with hyperlipidemia, and if seen, the patient should have screening for dyslipidemia.
The primary evaluation tool for dyslipidemia is a fasting lipid panel which consists of total cholesterol, LDL, HDL, and triglycerides. There is some debate on at what age dyslipidemia screening should start. The United States Preventative Services Task Force recommends screening all males 35 and older as well as high-risk males age 20 to 35. Also, all-woman 45 years and older as well as high-risk individuals 20 to 45 years of age. Other recommendations suggest getting fasting lipid panels for all individuals age 20 to 78 years at least every five years if no atherosclerotic disease is present.
Classification of dyslipidemia subdivides into five different categories, according to Frederickson phenotype. Phenotype I is an abnormality of chylomicrons and will result in triglycerides greater than 99 percentiles. Phenotype IIa consists mainly of LDL cholesterol abnormality and will have total cholesterol concentration greater than 90 percentile and possible apolipoprotein B greater than 90 percentile. Phenotype IIb consists of abnormality in LDL and very-low-density lipoprotein (VLDL) cholesterol. This type will result in total cholesterol and/or triglycerides greater than 90 percentile and apolipoprotein greater than 90 percentile. Phenotype III is an abnormality in VLDL remnants and chylomicrons, which results in elevated total cholesterol and triglycerides greater than 90 percentile. Phenotype IV is mainly when VLDL is abnormal and will result in total cholesterol greater than 90 percentile. This type can also present with triglycerides greater than 90 percentile and low HDL. Phenotype V is when chylomicrons and VLDL are abnormal, and triglycerides are greater than 99 percentiles.
Initial management for dyslipidemia involves lifestyle modifications. This approach should include a diet with an emphasis on the intake of vegetables, fruits, and whole grains within an appropriate calorie requirement. Also, adults should participate in moderate to vigorous aerobic physical activity 3 to 4 times a week for at least 40 minutes. First-line treatment for dyslipidemia is statins that inhibit 3-hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) reductase.
Patients with clinically significant atherosclerotic cardiovascular disease (ASCVD) (acute coronary syndromes, history of myocardial infarction, stable or unstable angina, arterial revascularization, and stroke) and are less than 75 years of age should be put on a high-intensity statin. Patients that are greater than 75 years of age with clinical ASCVD should be on a moderate-intensity statin. High-intensity statin therapy should start if the patient is 40 and 75 years old and has LDL-C greater than or equal to 190 mg/dL or has a history of diabetes and LDL-C between 70 to 189 mg/dL. Patients should be on a moderate or high-intensity statin if age 40 to 75 years old, LDL-C between 70 to 189 mg/dL, and have 10-year ASCVD greater than or equal to 7.5%. The clinician-patient discussion should be undertaken to discuss the introduction of high or moderate-intensity statin in situations such as less than 5% to 7.5% 10-year ASCVD risk.
For primary prevention, statin therapy should lower LDL-C approximately 30% to less than 50% with a moderate-intensity statin and greater than or equal to 50% with a high-intensity statin. High-intensity statins are atorvastatin 40 or 80 mg and rosuvastatin 20 mg. Some moderate-intensity statins atorvastatin 1 0mg, rosuvastatin 10 mg, simvastatin 20 mg or 40 mg, pravastatin 10 mg, etc.
For secondary prevention, as defined by a patient who has coronary artery disease, a target goal is set for LDL-C less than 70 mg/dL after being placed on a high-intensity statin for six weeks. If this goal is not met and LDL-C is significantly greater than 70, then combination therapy should be started in addition to high-intensity statin. If the patient is not high-risk, then the LDL-C goal should remain less than 70 mg/dL. If the patient is a high risk (already had acute coronary syndrome in the last year, familial hypercholesterolemia, diabetes, chronic kidney disease (stage 3 or 4), or atherosclerotic cardiovascular disease event, or the need for revascularization while on a statin), then the LDL goal should be less than 50 and if not met another agent should be added.
Currently, there are two classes of medications that are recommended with statin therapy because they have shown to decrease cardiovascular outcomes. One of these is ezetimibe, which inhibits the absorption of cholesterol. This drug can lower LDL-C an additional 25% in combination with statin therapy.
Another category targets proprotein convertase subtilisin/kexin type 9 (PCSK9), which regulates the LDL receptor. An increase in PSCK9 decreases LDL receptors and therefore increases LDL levels in the blood. PCSK9 inhibitors are monoclonal antibodies that bind PCSK9 and, in doing so, decrease LDL-C levels.
The new agent inclisiran is an interfering ribonucleic acid drug that stops the production of PCSK9 with twice a yearly dosing. This agent may be beneficial in patients who are intolerant of LDL lowering medications. As of this writing, it has not yet received FDA approval in the USA.
Icosapent ethyl is an FDA approved medication that has been shown to reduce cardiovascular risk in patients with elevated triglycerides in addition to maximal statin therapy.
Bempedoic acid is another drug that is an option for people intolerant to statins in combination with ezetimibe. This drug works by inhibiting adenosine triphosphate citrate lyase, which helps make cholesterol in the liver and therefore decreasing levels. Many other new and exciting medications are in current research to help lower cholesterol levels and prevent cardiovascular events.
Other categories of treatment that have not been shown to reduce cardiovascular events but have been useful in dyslipidemia therapy are bile acid sequestrants such as cholestyramine, colestipol, and colesevelam, which decrease bile acid reabsorption, therefore, increasing clearance of LDL-C and decreasing levels. Fibric acid derivatives (fibrates) are peroxisome proliferator-activated receptor agonists. These have shown to increase HDL-C and reduce triglycerides. However, in combination with statins can increase the risk of myopathy and rhabdomyolysis, which can cause generalized muscle pain. Current guidelines recommend against the use of statins and gemfibrozil. Niacin has shown to increase HDL and reduce VLDL, which also decreases LDL but has a significant side effect profile with the greatest being flushing. Taking aspirin can decrease the occurrence of this side effect.
One tool that clinicians can use to calculate the prognosis of a patient with dyslipidemia is 10-year atherosclerotic cardiovascular disease risk. This calculator factors in risk for patients based on lipid levels as well as age, race, tobacco use, diabetes, sex, and hypertension history. This calculation will give a percentage of risk that a cardiovascular event will happen in 10 years. Also, a percentage of risk if risk factors were optimal.
The most significant complication for dyslipidemia is cardiovascular disease. Complications of this include sudden cardiac death, acute myocardial infarction, or stroke. Multiple studies have demonstrated that statin and appropriate dyslipidemia treatment has significantly reduced the risk of all-cause mortality, cardiovascular events, and cardiovascular mortality.
As discussed above, patients need to recognize and adhere to specific health behaviors that can maintain and lower lipid levels. These include, but are not limited to, weight control, which includes a heart-healthy diet and exercise as well as avoidance of tobacco. Patients should also engage in conversation with their primary care providers on when to start getting screened or when to initiate treatment, as stated above.
Enhancing healthcare outcomes for patients with dyslipidemia has to involve a multidisciplinary treatment team, including clinical physicians such as cardiologists or endocrinologists, nurses, and pharmacists. Clinicians have to be aware of up to date guidelines on lipid screening, indication for treatment, and goals LDL-C levels. Nurses should adhere to the same awareness as physicians but also aid in maintaining close follow up with these patients to help improve adherence to medications. Pharmacists can assist in watching for drug interactions, counseling regarding potential adverse effects, and providing dosing instruction.
|||Rader DJ,Hoeg JM,Brewer HB Jr, Quantitation of plasma apolipoproteins in the primary and secondary prevention of coronary artery disease. Annals of internal medicine. 1994 Jun 15; [PubMed PMID: 8185133]|
|||Mozaffarian D,Benjamin EJ,Go AS,Arnett DK,Blaha MJ,Cushman M,Das SR,de Ferranti S,Després JP,Fullerton HJ,Howard VJ,Huffman MD,Isasi CR,Jiménez MC,Judd SE,Kissela BM,Lichtman JH,Lisabeth LD,Liu S,Mackey RH,Magid DJ,McGuire DK,Mohler ER 3rd,Moy CS,Muntner P,Mussolino ME,Nasir K,Neumar RW,Nichol G,Palaniappan L,Pandey DK,Reeves MJ,Rodriguez CJ,Rosamond W,Sorlie PD,Stein J,Towfighi A,Turan TN,Virani SS,Woo D,Yeh RW,Turner MB, Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016 Jan 26; [PubMed PMID: 26673558]|
|||Defesche JC,Gidding SS,Harada-Shiba M,Hegele RA,Santos RD,Wierzbicki AS, Familial hypercholesterolaemia. Nature reviews. Disease primers. 2017 Dec 7; [PubMed PMID: 29219151]|
|||Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol--United States, 1999-2002 and 2005-200. MMWR. Morbidity and mortality weekly report. 2011 Feb 4; [PubMed PMID: 21293326]|
|||Lugo-Somolinos A,Sánchez JE, Xanthomas: a marker for hyperlipidemias. Boletin de la Asociacion Medica de Puerto Rico. 2003 Jul-Aug; [PubMed PMID: 15032023]|
|||Kopin L,Lowenstein C, Dyslipidemia. Annals of internal medicine. 2017 Dec 5; [PubMed PMID: 29204622]|
|||Fredrickson DS, An international classification of hyperlipidemias and hyperlipoproteinemias. Annals of internal medicine. 1971 Sep [PubMed PMID: 5568160]|
|||Eckel RH,Jakicic JM,Ard JD,de Jesus JM,Houston Miller N,Hubbard VS,Lee IM,Lichtenstein AH,Loria CM,Millen BE,Nonas CA,Sacks FM,Smith SC Jr,Svetkey LP,Wadden TA,Yanovski SZ, 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology. 2014 Jul 1; [PubMed PMID: 24239922]|
|||Stone NJ,Robinson JG,Lichtenstein AH,Bairey Merz CN,Blum CB,Eckel RH,Goldberg AC,Gordon D,Levy D,Lloyd-Jones DM,McBride P,Schwartz JS,Shero ST,Smith SC Jr,Watson K,Wilson PW, 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology. 2014 Jul 1; [PubMed PMID: 24239923]|
|||Vavlukis M,Vavlukis A, Adding ezetimibe to statin therapy: latest evidence and clinical implications. Drugs in context. 2018; [PubMed PMID: 30023003]|
|||Karr S, Epidemiology and management of hyperlipidemia. The American journal of managed care. 2017 Jun; [PubMed PMID: 28978219]|
|||Mills EJ,O'Regan C,Eyawo O,Wu P,Mills F,Berwanger O,Briel M, Intensive statin therapy compared with moderate dosing for prevention of cardiovascular events: a meta-analysis of >40 000 patients. European heart journal. 2011 Jun; [PubMed PMID: 21385791]|
|||Ray KK,Bays HE,Catapano AL,Lalwani ND,Bloedon LT,Sterling LR,Robinson PL,Ballantyne CM, Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. The New England journal of medicine. 2019 Mar 14 [PubMed PMID: 30865796]|
|||Muntner P,Colantonio LD,Cushman M,Goff DC Jr,Howard G,Howard VJ,Kissela B,Levitan EB,Lloyd-Jones DM,Safford MM, Validation of the atherosclerotic cardiovascular disease Pooled Cohort risk equations. JAMA. 2014 Apr 9; [PubMed PMID: 24682252]|
|||Chou R,Dana T,Blazina I,Daeges M,Jeanne TL, Statins for Prevention of Cardiovascular Disease in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2016 Nov 15; [PubMed PMID: 27838722]|