High Cholesterol: Symptoms, Causes, Tests, and Treatment

High cholesterol, or hypercholesterolemia, is one of the most important modifiable risk factors for cardiovascular disease. Cholesterol is an essential lipid for the body, as it participates in the synthesis of cell membranes, hormones, and vitamin D. However, when its levels, especially LDL cholesterol increase, it contributes to the development of atherosclerosis.

Atherosclerosis is characterized by the deposition of lipids in the walls of arteries, leading to narrowing and an increased risk of myocardial infarction and stroke. Importantly, hypercholesterolemia is usually silent, with no obvious symptoms for many years.

In this context, prevention and early diagnosis through specialized testing become crucial, particularly when combined with a more comprehensive approach such as that of Functional Medicine.

Epidemiological Data

Hypercholesterolemia is a global public health issue. In Europe, elevated LDL cholesterol levels remain among the leading risk factors for cardiovascular morbidity and mortality. According to recent studies, cardiovascular disease continues to be the leading cause of death in Europe, with dyslipidemia playing a significant role. It is estimated that a large proportion of the adult population has elevated cholesterol levels, while a significant percentage remains undiagnosed or inadequately managed. Familial hypercholesterolemia, a genetic form of the condition, occurs in approximately 1 in 250 individuals in the general population.

In Greece, epidemiological data indicate a high prevalence of dyslipidemia, particularly among individuals with sedentary lifestyles, poor dietary habits, and increased body weight. The shift from the traditional Mediterranean diet toward more Westernized dietary patterns has significantly contributed to the rise in cases.

Symptoms and Signs

High cholesterol is often referred to as a “silent disease,” as it typically does not cause noticeable symptoms until complications arise. However, in some cases, the following may appear:

Xanthomas: Deposits of lipids under the skin, often on tendons or around joints. They are indicative of severe and often genetic hypercholesterolemia.
Xanthelasmas: Yellowish plaques on the eyelids associated with lipid disorders.
Arcus senilis (or Corneal arcus): A whitish ring around the cornea, particularly in younger individuals.

Beyond these, the first “symptoms” are often related to complications, such as angina (due to coronary artery disease), myocardial infarction, or stroke. This highlights the importance of preventive screening, even in individuals without symptoms.

Underlying Causes

Hypercholesterolemia is not a single-factor condition. Instead, it results from the interaction of genetic, metabolic, and environmental factors.

Genetic factors: Familial hypercholesterolemia is caused by mutations in genes involved in LDL metabolism, such as the LDL receptor gene. This leads to reduced clearance of LDL from the blood and extremely high levels from a young age, dramatically increasing cardiovascular risk.
Diet: High intake of saturated and trans fats contributes to increased LDL cholesterol. Diets rich in processed foods, sugar, and low-quality fats negatively affect the lipid profile and promote inflammation.
Sedentary lifestyle: Lack of physical activity leads to reduced HDL cholesterol and increased LDL. At the same time, it negatively impacts insulin sensitivity and overall metabolism.
Metabolic disorders: Conditions such as type 2 diabetes and metabolic syndrome are associated with elevated triglycerides and reduced HDL, contributing to an atherogenic lipid profile.
Hormonal disorders: Hypothyroidism can lead to increased LDL cholesterol due to reduced lipid metabolism. Similarly, other endocrine disorders can affect lipid balance.
Inflammation and oxidative stress: Chronic low-grade inflammation and oxidative stress contribute to the oxidation of LDL, making it more atherogenic and accelerating the process of atherosclerosis.

Laboratory Tests for Evaluating Hypercholesterolemia

Proper assessment of high cholesterol goes beyond a simple measurement. A comprehensive approach is required, including both conventional and more specialized analyses, particularly within Functional Medicine.

(a) Conventional Laboratory Tests

Total Cholesterol (TC): The total amount of cholesterol in the blood. Provides a general overview but is insufficient alone for risk assessment.
LDL Cholesterol (LDL-C): The “bad” cholesterol. Transports cholesterol from the liver to tissues and contributes to atherosclerosis when elevated.
HDL Cholesterol (HDL-C): The “good” cholesterol. Helps remove excess cholesterol from circulation.
Triglycerides (TG): A form of energy storage. Elevated levels are associated with metabolic syndrome and increased cardiovascular risk.
Non-HDL Cholesterol: Includes all atherogenic lipoproteins and is considered a more reliable risk marker than total cholesterol.
Apolipoprotein B (ApoB): Reflects the number of atherogenic particles (LDL and VLDL), offering a more precise risk assessment than LDL alone.

(b) Functional Medicine Tests

Lipoprotein(a) – Lp(a): An independent cardiovascular risk marker. Elevated levels increase atherosclerosis risk independently of LDL.
Lipoprotein(a), A5673G Mutation: A genetic polymorphism affecting Lp(a) regulation, useful for risk stratification and personalized interventions.
Comprehensive Hyperlipidemia Genetic Testing using NGS (Next Generation Sequencing): In cases of persistent or severe hypercholesterolemia, particularly when accompanied by a strong family history, premature cardiovascular disease, or disproportionately elevated Lp(a) levels, a more extensive genetic evaluation using NGS technology may be recommended. This approach enables the simultaneous analysis of multiple genes associated with inherited dyslipidemias and lipid metabolism disorders, contributing to a more accurate cardiovascular risk assessment and supporting more personalized therapeutic interventions.
Oxidized LDL (oxLDL): Measures oxidized LDL, indicating oxidative stress and active atherosclerosis.
hs-CRP: High-sensitivity C-reactive protein, assessing low-grade inflammation.
Homocysteine: A metabolic marker linked to endothelial damage and nutritional deficiencies.
ΩmegaScan®: Analysis of fatty acid composition, reflecting diet, inflammation, and cellular function.
Glucose and Insulin, HOMA-IR index: Evaluation of insulin resistance, closely linked to lipid disorders.

(c) Other Tests (Imaging and Additional)

Carotid ultrasound (Triplex): Detects atherosclerotic plaques and intima-media thickness.
Coronary CT angiography: Identifies calcified plaques in coronary arteries.
Stress test: Assesses cardiac function under exertion.
Echocardiography (Cardiac ultrasound): Evaluates heart structure and function.

Therapeutic Approaches to Hypercholesterolemia

Management requires a multifactorial strategy combining medical treatments with lifestyle interventions.

(a) Conventional Treatments
Pharmacological interventions constitute a cornerstone in the management of hypercholesterolemia, particularly in individuals at high cardiovascular risk or in cases where lifestyle modifications alone are insufficient.

Statins: Inhibit HMG-CoA reductase, reducing cholesterol synthesis and increasing LDL clearance. First-line therapy. Possible side effects include muscle pain and elevated liver enzymes.
Ezetimibe: Reduces intestinal cholesterol absorption, often combined with statins.
PCSK9 inhibitors: Injectable drugs that significantly lower LDL levels, especially in high-risk patients.
Fibrates: Mainly reduce triglycerides and increase HDL.
Bile acid sequestrants: Bind bile acids in the intestine, increasing cholesterol utilization.
Newer therapies: Inclisiran and bempedoic acid, targeting different pathways.

Despite the effectiveness of medications, relying exclusively on pharmacological treatment without addressing the underlying causes is often inadequate for achieving optimal long-term health outcomes.

(b) Natural Approaches
The Functional Medicine approach places particular emphasis on natural interventions aimed at correcting the root causes of dyslipidemia.

Diet
Diet is the most important modifiable factor. A Mediterranean-style dietary pattern has been shown to reduce LDL cholesterol levels and cardiovascular risk. It is characterized by high consumption of olive oil, vegetables, fruits, legumes, nuts, and fish, along with reduced intake of red meat and processed foods. Increased dietary fiber intake contributes to reduced cholesterol absorption, while omega-3 fatty acids exert anti-inflammatory effects and improve the lipid profile. In contrast, the consumption of saturated and trans fats significantly increases LDL cholesterol levels. Personalized nutrition plans, based on metabolic markers and functional medicine testing, may provide even greater benefits.

Lifestyle
Regular physical activity improves HDL cholesterol, reduces triglycerides, and enhances cardiorespiratory fitness. A combination of aerobic exercise and resistance training totaling at least 150 minutes per week is recommended. Stress management is also critical, as chronic stress affects lipid metabolism through hormonal mechanisms. Adequate sleep and smoking cessation are essential components for improving the lipid profile.

Supplements and Herbal Therapies
Certain supplements have demonstrated beneficial effects in lowering cholesterol levels:

Omega-3 fatty acids: Primarily contribute to triglyceride reduction. Typical dosages range from 1 to 4 grams daily. Mild gastrointestinal disturbances may occur, and caution is advised in individuals taking anticoagulant medications.
Plant sterols and stanols: Reduce intestinal cholesterol absorption. A daily intake of approximately 2 grams is generally recommended. They are considered safe for most individuals.
Red yeast rice: Contains naturally occurring statin-like compounds and may help lower LDL cholesterol. Its use should be monitored carefully, as it may produce side effects similar to pharmaceutical statins.
Berberine: A plant alkaloid that improves glucose metabolism and reduces cholesterol levels. It is commonly administered at doses of 500 mg two to three times daily. Gastrointestinal side effects may occur.
Soluble fibers such as psyllium: Contribute to LDL cholesterol reduction. An intake of 5–10 grams daily is generally recommended, along with adequate hydration.

The use of supplements should always be supervised by a qualified healthcare professional, particularly in individuals already receiving pharmacological treatment.

In Conclusion

Comprehensive management of hypercholesterolemia requires personalization. Functional Medicine testing can help identify the underlying causes, enabling targeted interventions that go beyond symptom suppression.

References

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