Background

Dyslipidemia is characterized by abnormal levels of lipids in the blood. Lipids include cholesterol and triglycerides, which are essential for various physiological functions in the body but can become challenging when their levels are imbalanced. Dyslipidemia is a significant risk factor for cardiovascular diseases, including coronary artery disease and stroke.

Dyslipidemia is often associated with other health conditions such as diabetes, obesity, and metabolic syndrome. Certain risk factors contribute to the development of dyslipidemia, including unhealthy diet, lack of physical activity, smoking, and genetics. Early detection allows for timely intervention and management to prevent complications. 

Epidemiology

Dyslipidemia is a common health issue worldwide, affecting a significant proportion of the population. The prevalence of dyslipidemia tends to increase with age. Dyslipidemia is a significant contributor to the global burden of cardiovascular diseases, including coronary artery disease and stroke.

Lifestyle factors, dietary habits, and genetic predisposition contribute to these geographical variations. Men tend to have higher cholesterol levels than premenopausal women, but the risk for women increases after menopause.

There may be disparities in the prevalence and management of dyslipidemia among different socioeconomic groups. Dyslipidemia contributes significantly to the overall burden of non-communicable diseases and places a strain on healthcare systems. Changes in lifestyle, healthcare policies, and treatment options can influence these trends. 

Anatomy

Pathophysiology

The pathophysiology of dyslipidemia is multifaceted and often influenced by a combination of genetic, environmental, and lifestyle factors. Dietary intake, particularly high consumption of saturated and trans fats, can contribute to elevated low-density lipoprotein (LDL) cholesterol levels, commonly known as bad cholesterol. Additionally, a sedentary lifestyle and excess body weight may exacerbate dyslipidemia by reducing high-density lipoprotein (HDL) cholesterol or good cholesterol.

Genetic predisposition plays a significant role, as certain individuals may have inherent abnormalities in lipid metabolism. Dyslipidemia is associated with impaired clearance of lipids from the bloodstream, leading to the accumulation of LDL cholesterol and triglycerides in arterial walls. This accumulation initiates the formation of atherosclerotic plaques, which narrow and stiffen arteries, ultimately impairing blood flow.

The inflammatory response triggered by these plaques further contributes to the progression of atherosclerosis. As atherosclerosis advances, the risk of cardiovascular events such as heart attacks and strokes increase. Dyslipidemia is often part of a broader clinical picture, interacting with conditions like diabetes and metabolic syndrome, creating a synergistic effect on cardiovascular risk. 

Etiology

Various health behaviors contribute to elevated lipid levels, with factors such as tobacco use, nutrition, sedentary lifestyle, and obesity playing significant roles. Nutrition-related risk factors encompass inadequate intake of fruits, nuts/seeds, and vegetables, as well as excessive consumption of saturated fats.

Dyslipidemia can also result from familial disorders, notably familial hypercholesterolemia, where autosomal dominant mutations predominantly affect LDL receptors, leading to heightened LDL-C levels. While less common, other mutations within the cholesterol pathway have been identified as contributors to dyslipidemia. 

Genetics

Prognostic Factors

The prognosis of dyslipidemia largely depends on various factors, including the severity of the condition, the presence of other cardiovascular risk factors, and the effectiveness of management and treatment strategies. 

Clinical History

Gathering a comprehensive history is crucial for identifying individuals at high risk for dyslipidemia. Specifically, the social history should encompass details such as tobacco use and specific dietary habits. In the past medical history, it is essential to identify patients requiring primary prevention versus secondary prevention when considering the initiation of statin therapy.

Additionally, family history plays a crucial role in recognizing conditions like familial hypercholesterolemia. Individuals with a family history of dyslipidemia or cardiovascular disease may have a higher risk. Factors such as a sedentary lifestyle, poor diet, obesity, diabetes, and smoking can contribute to dyslipidemia.

Dyslipidemia is often asymptomatic. Symptoms may arise when dyslipidemia leads to complications, such as chest pain, heart attack, stroke, or peripheral arterial disease. Dyslipidemia is often a chronic condition that develops over time. Some individuals may have a genetic predisposition to dyslipidemia, leading to an earlier onset. Diet modification, regular exercise, and maintaining a healthy weight can help manage dyslipidemia. 

Physical Examination

The physical examination has its limitations in detecting dyslipidemia disorders. Xanthomas refer to lipid deposits that manifest on the skin and occasionally in the subcutaneous tissue.

Exhibiting a yellowish hue, they can take the form of plaques, nodules, or lesions. Xanthomas may appear on the palmar crease, indicating a potential link to familial dysbetalipoproteinemia, or on areas such as the eyelids or tendons.

Typically associated with hyperlipidemia, the presence of xanthomas should prompt screening for dyslipidemia in the affected patient. 

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

• Hypothyroidism 
• Biliary obstruction 
• Nephrotic syndrome 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The management of dyslipidemia primarily involves a multifaceted approach, starting with lifestyle modifications. Patients are encouraged to adopt a heart-healthy diet that emphasizes the intake of vegetables, fruits, and whole grains, while adhering to an appropriate caloric intake. Regular aerobic physical activity, ranging from moderate to vigorous intensity, is recommended three to four times a week for at least 40 minutes per session.

These lifestyle changes aim to improve lipid profiles and reduce cardiovascular risk. In cases where lifestyle measures are insufficient or impractical, pharmacological interventions may be considered. Statins, a commonly prescribed class of drugs, play a central role in lowering LDL cholesterol levels. For individuals who require further reduction or cannot tolerate statins, newer agents such as bempedoic acid and inclisiran may be explored.

Patient-specific factors, including comorbidities and individual response to treatment, guide the choice of medications. Regular monitoring and follow-up assessments are integral to assess the effectiveness and safety of the chosen interventions, ensuring a comprehensive and personalized approach to dyslipidemia management. 

Administration of Statins 

Statins primarily work by inhibiting an enzyme called HMG-CoA reductase, which is involved in cholesterol synthesis in the liver. By reducing cholesterol production, statins lower the levels of LDL cholesterol in the bloodstream. Statins have been shown to reduce the risk of cardiovascular events, such as heart attacks and strokes, especially in individuals with a history of cardiovascular disease or those at high risk.

While statins primarily target LDL cholesterol, they may also have a modest impact on lowering triglyceride levels and increasing high-density lipoprotein (HDL) cholesterol, often referred to as “good” cholesterol. Statins are typically administered orally in the form of tablets or capsules. They are usually taken once daily, preferably in the evening, as cholesterol synthesis in the liver is typically higher during the night. Dosages may vary depending on the specific statin prescribed, the patient’s lipid profile, and overall health.

For primary prevention, it is recommended that statin therapy achieve a reduction in LDL-C levels of about 30% to less than 60% when using a moderate-intensity statin and greater than or equal to 50% when employing a high-intensity statin. High-intensity statins encompass atorvastatin at 40 or 80 mg and rosuvastatin at 20 mg. Meanwhile, some examples of moderate-intensity statins include rosuvastatin, atorvastatin, simvastatin, pravastatin, and others. Individuals with a history of cardiovascular events, such as heart attacks or strokes, may be prescribed statins for secondary prevention to reduce the risk of future events.  

Administration of adenosine triphosphate-citrate lyase (ACL) inhibitor 

It is an oral, once-daily medication that was developed to provide an additional option for individuals who require further reduction in LDL-C levels despite statin therapy or for those who cannot tolerate statins. Bempedoic acid works by inhibiting ATP-citrate lyase, an enzyme involved in cholesterol synthesis in the liver.

By blocking this enzyme, bempedoic acid reduces the production of cholesterol, leading to a decrease in LDL-C levels. In addition to lowering LDL-C levels, bempedoic acid has been studied for its potential cardiovascular benefits. Clinical trials have investigated its impact on reducing major cardiovascular events in high-risk individuals.

Bempedoic acid is sometimes prescribed in combination with ezetimibe, another medication that reduces cholesterol absorption in the intestine. Bempedoic acid is generally not recommended for individuals with a history of allergic reactions, active liver disease, or unexplained persistent elevations in liver enzymes. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

lifestyle-modifications

The initial management strategy for dyslipidemia prioritizes lifestyle modifications. This plan encompasses adopting a dietary pattern that underscores the consumption of vegetables, fruits, and whole grains while adhering to an appropriate caloric intake.

Additionally, adults are advised to engage in moderate to vigorous aerobic physical activity three to four times weekly, with each session lasting at least 40 minutes. 

Administration of other pharmaceutical agents

Inclisiran, a novel agent, operates as an interfering ribonucleic acid drug, effectively halting the production of PCSK9, and it requires semiannual dosing. This therapeutic approach holds promise for individuals intolerant to LDL-lowering medications.

However, it is important to note that, as of the current date, inclisiran still needs to secure FDA approval in the United States. On the other hand, icosapent ethyl is an FDA-approved medication demonstrated to mitigate cardiovascular risk in patients with elevated triglyceride levels, mainly when administered alongside maximal statin therapy. 

Medication

Future Trends

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References