Approximately 86 million and 56.9 million American adults have high cholesterol and triglycerides, respectively. Patients with hyperlipidemia are about twice as likely to develop cardiovascular disease than those without. However, treating elevated lipids has been shown to significantly improve the risk of cardiovascular disease, adverse cardiovascular events, and cardiovascular-related death.

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The Basics of Hyperlipidemia

Hyperlipidemia, also known as dyslipidemia or high cholesterol, is simply defined as having elevated levels of lipids (fats) in the bloodstream. Lipids are fatty chemical compounds that don't dissolve in water. In the context of hyperlipidemia, we primarily refer to three types of lipids: low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides.

LDL cholesterol (LDL-C), often referred to as "bad" cholesterol, is the fraction of cholesterol carried in the blood by low-density lipoproteins (think of lipoproteins as cholesterol shuttles). LDL transports LDL-C from the liver to and delivers it to peripheral cells. While cholesterol is essential for cellular function, LDL-C is easily oxidized in the arteries and is a primary culprit in plaque formation and atherosclerosis. Too much LDL-C is associated with an increased risk of cardiovascular disease (CVD). (15) 

HDL cholesterol (HDL-C) is the fraction of cholesterol carried by high-density lipoproteins. HDL-C is often called "good" cholesterol because HDL acts like a vacuum, sweeping up excess cholesterol in cells and taking it back to the liver for recycling and elimination. HDL is antiatherogenic and anti-inflammatory because it prevents the buildup of plaques in the arteries. When HDL-C levels are low (as often is the case in the presence of high LDL-C and triglycerides), the removal of cholesterol is compromised, resulting in increased cholesterol accumulation in blood vessels and the formation of atherosclerotic plaques. According to the CDC, 19% of all adults had low HDL-C between 2011 and 2014. (15) 

Triglycerides (TG) are a form of fat derived from dietary sources or the conversion of carbohydrates. They are stored in adipose tissue and used for energy. Hypertriglyceridemia (elevated triglycerides) affects one in five American adults and is strongly associated with an increased risk of CVD, heart attack, stroke, and all-cause mortality. (15)

Recognizing the Symptoms of Hyperlipidemia

In its early stages, hyperlipidemia itself does not typically present with noticeable symptoms. It is often referred to as a "silent" condition because individuals may not be aware of their elevated cholesterol/triglyceride levels until it leads to complications, such as heart disease or stroke. Instead of manifesting direct symptoms, hyperlipidemia contributes to the development of atherosclerosis, a process where cholesterol and other substances accumulate in the walls of arteries, forming plaques. Atherosclerotic plaques cause arteries to narrow, blocking blood flow, and can burst, leading to blood clots. 

People with very high cholesterol levels may get waxy, fatty plaques on their skin (called xanthomas) or opaque cholesterol rings around their irises (called corneal arcus). Most times, however, the physical signs that arise from hyperlipidemia are usually associated with the complications of atherosclerosis. For instance, chest pain, shortness of breath, or fatigue may occur in individuals with coronary artery disease (CAD) resulting from narrowed arteries. A stroke, caused by reduced blood flow to the brain due to atherosclerotic plaques, can lead to symptoms like sudden numbness, confusion, difficulty speaking, headache, and a loss of coordination.

Given the asymptomatic nature of high cholesterol, regular screening and awareness of individual risk factors, such as family history and lifestyle choices, are key in proactively managing and preventing the progression of this condition.

Causes and Risk Factors of Hyperlipidemia

There are two main classifications of hyperlipidemia: familial (primary) and acquired (secondary). 

Familial combined hyperlipidemia (FCH) is one of the most common hereditary lipid disorders. It is characterized by elevated levels of total cholesterol, LDL-C, TG, and decreased levels of HDL-C due to a genetic predisposition for causing an overproduction of lipoproteins by the liver. People with FCH develop high cholesterol and triglycerides as teenagers. FCH is correlated to an increased risk of early CAD, heart attack, obesity, and glucose intolerance. (18) 

Acquired hyperlipidemia is the result of underlying health conditions, medications, and lifestyle choices. Medical conditions that can increase lipids include hypothyroidism, diabetes, kidney disease, and liver disease. Medications associated with causing abnormal lipid levels include birth control pills, corticosteroids, diuretics, antiretrovirals, and beta-blockers. Lifestyle factors that increase the risk for high cholesterol and triglyceride levels include an unhealthy diet, a sedentary lifestyle, smoking and exposure to tobacco smoke, and being overweight or obese.  

Testing and Diagnosis

The first step in diagnosing hyperlipidemia involves ordering blood tests that measure lipid levels. A basic lipid panel includes four standard biomarkers: total cholesterol (TC), LDL-C, HDL-C, and TG. The normal levels for each of these tests are: 

• TC: less than 200 mg/dL
• LDL-C: less than 100 mg/dL
• HDL-C: higher than 60 mg/dL
• TG: less than 150 mg/dL

Lipid panel results guide the diagnosis of hyperlipidemia. According to the Adult Treatment Panel III (ATP III) guidelines, hyperlipidemia is defined by specific lipid profile parameters: elevated levels of TC, LDL-C, and/or TG. Low levels of HDL-C typically accompany the diagnosis.

Recent research has illuminated the limitations of relying solely on basic lipid profile biomarkers in assessing cardiovascular risk. While traditional measures like LDL-C provide valuable insights, they may not fully capture the intricacies of lipid metabolism and cardiovascular health. Newer studies emphasize the significance of alternative markers such as LDL particle (LDL-P) number, apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)] in refining risk stratification and predicting cardiovascular outcomes. These advanced markers, included in an advanced lipid panel, offer a more comprehensive view of lipid-related risk factors, considering factors beyond cholesterol quantity. (22)

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Treatment Options for Hyperlipidemia

A heart-healthy diet plays a pivotal role in preventing and managing hyperlipidemia. The Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets, rich in fruits, vegetables, whole grains, and lean proteins, have shown significant efficacy in supporting cardiovascular health. Incorporating these dietary patterns has been associated with reductions in lipid parameters and adverse cardiovascular outcomes. For instance, studies have demonstrated that adherence to the Mediterranean diet can optimize lipid profiles in patients with familial and acquired hyperlipidemia by improving HDL function and reducing TC, LDL-C, ApoB, and inflammation. Translating to cardiovascular outcomes, the Mediterranean diet has been shown to reduce the risk of all cardiovascular diseases by 61% and lower cardiovascular mortality risk by 29%.

Regular physical activity is another cornerstone in the prevention and management of hyperlipidemia. Engaging in aerobic exercises such as brisk walking, running, or cycling has been linked to increased HDL-C levels and functionality, along with reductions in TGs and LDL-C. Obesity is linked to higher fasting plasma TGs and LDL-C and low HDL-C. Regular physical activity supports weight loss and maintenance of healthy weight. The American Heart Association (AHA) recommends that adults get at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic activity weekly, in addition to at least two sessions of strength training per week.

Quitting smoking is a crucial component in the multifaceted approach to managing hyperlipidemia and reducing cardiovascular risk. Smoking is not only a major risk factor for atherosclerosis but also exacerbates the adverse effects of dyslipidemia. The prevalence of dyslipidemia among current smokers (54.9%) surpasses that of former smokers (43.9%). Former smokers exhibit a higher prevalence compared to non-smokers (38.0%). Smoking cessation leads to favorable changes in lipid profiles and substantially lowers the risk of heart disease and stroke. Within just one year of quitting, the risk of dying from coronary heart disease decreases by half and continues to decline over time.

Pharmacologic treatments for hyperlipidemia can be used for primary and secondary prevention of CVD in conjunction with the lifestyle modifications discussed above. Medical guidelines recommend initiating statin therapy when an individual has a history of atherosclerotic cardiovascular disease (ASCVD) or if their LDL-C levels exceed specific thresholds based on age, diabetes status, and other risk factors. Statins reduce LDL-C by inhibiting HMG-CoA reductase, a key enzyme involved in cholesterol synthesis. Statins have demonstrated robust efficacy, resulting in a 25-60% reduction in LDL-C and a 24-37% risk reduction for CVD. However, potential side effects, such as muscle pain and liver enzyme elevation, may interfere with medication compliance.

For patients who are statin-intolerant or do not meet desired LDL-C targets with statin therapy alone, other nonstatin pharmacologic therapies are available. Ezetimibe inhibits cholesterol absorption in the small intestine and is often used with statins for additive effects. It can lower LDL-C levels by up to 20%. Combining a statin with ezetimibe is more effective in attaining LDL-C goals than statin monotherapy. Ezetimibe's most common side effects include headache, runny nose, and sore throat. (55, 57) 

PCSK9 inhibitors are another newer class of very well-tolerated nonstatin lipid-lowering medication. They bind to proprotein convertase subtilisin/kexin type 9 (PCSK9), preventing its interaction with LDL receptors and consequently enhancing LDL-C clearance from the bloodstream. This class of drug effectively reduces the risk of major adverse cardiovascular events and favorably modifies lipid profiles by reducing LDL-C, TG, TC, Lp(a), and ApoB.

Fibrates target triglyceride levels by activating peroxisome proliferator-activated receptors (PPARs). They effectively reduce triglycerides and modestly elevate HDL-C. While fibrates are generally well-tolerated, side effects may include elevated liver enzymes, gastrointestinal disturbances, and, infrequently, an increased risk of muscle pain when combined with statins. 

Managing Hyperlipidemia: A Comprehensive Approach

Managing hyperlipidemia requires a comprehensive approach that extends beyond merely prescribing medications to lower cholesterol levels. It encompasses a multifaceted and integrative strategy addressing various aspects of patient care, emphasizing regular monitoring of lipid levels, addressing co-existing conditions, and educating patients on the significance of treatment adherence and lifestyle modifications. Regular lipid screenings allow healthcare providers to track progress, adjust treatment plans, and intervene promptly to prevent complications associated with uncontrolled hyperlipidemia. Effective management also involves managing co-existing conditions such as hypertension, diabetes, and obesity, which often coexist with hyperlipidemia and contribute to cardiovascular risk. 

Patient education empowers individuals to actively participate in their health management. Educating patients about the importance of adhering to treatment regimens and adopting heart-healthy behaviors can significantly impact lipid profiles and reduce cardiovascular risk. Studies show that patient education encourages healthy behaviors, improves patient quality of life and health outcomes, and lowers healthcare-related costs. Conversely, a lack of education increases health complications and healthcare costs. 

Integrative cardiology represents a comprehensive management strategy for cardiovascular health that extends beyond conventional medical interventions, emphasizing the collaboration of various healthcare disciplines to optimize patient outcomes. Integrative cardiology involves forming a multi-modal healthcare team, which may include cardiologists, nutritionists, exercise physiologists, and mind-body practitioners. This collaborative approach aims to address the complexity of cardiovascular conditions by using standard medical treatments and incorporating complementary therapies such as acupuncture, yoga, and dietary supplements. This approach provides personalized and patient-centered care by blending evidence-based conventional and complementary practices to consider the physical, mental, and emotional aspects of heart health. Ultimately, it enhances the overall effectiveness of care by offering patients individualized treatment plans that may lead to improved outcomes and a higher quality of life.

Prevention and Early Intervention

The prevention of hyperlipidemia begins with public health measures that promote awareness, education, and lifestyle modifications at a population level. Public health campaigns advocating for heart-healthy diets, regular physical activity, and smoking cessation can significantly reduce the overall incidence of hyperlipidemia. Public health initiatives aimed at educating the public on the modifiable risk factors for CVD and providing access to healthy food choices and healthcare services are crucial for preventing lipid abnormalities.

Genetic counseling and screening are particularly important for families with a history of hyperlipidemia. It is the role of primary care providers to identify individuals at a higher genetic risk so that early screening, diagnosis, and personalized interventions can be implemented to prevent the long-term consequences of unmanaged hyperlipidemia. The United States Preventive Services Task Force (USPSTF) recommends that adults at risk for coronary heart disease be screened for lipid disorders starting as young as 20 years old.

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Key Takeaways

Understanding, diagnosing, and managing hyperlipidemia is crucial for preventing cardiovascular disease. Elevated levels of cholesterol and triglycerides, if left unaddressed, can contribute to atherosclerosis and increase the risk of heart disease and stroke. Diagnosis involves lipid profile assessments, focusing on LDL cholesterol, HDL cholesterol, and triglyceride levels. An integrative approach to management includes lifestyle modifications such as a heart-healthy diet, regular exercise, and smoking cessation, alongside pharmacologic interventions like statins and other lipid-lowering medications. Individuals need to recognize the importance of early detection through regular screenings and the impact of lifestyle choices on lipid profiles. Consulting with healthcare professionals is paramount for personalized advice and tailored treatment plans, emphasizing that hyperlipidemia is a manageable condition when addressed proactively.