What causes high cholesterol?

Hyperlipidemia or dyslipidemia, generalized as high cholesterol, is characterized by elevated blood serum levels of low-density lipoprotein (LDL) and triglycerides and low levels of high-density lipoprotein (HDL).1 All of these measurements together are known as total cholesterol (TC).  

Table 1. Recommended cholesterol levels for otherwise healthy adults presented in mg/dL^1,2 

There are several causes of hyperlipidemia, including heritable traits (e.g., familial dyslipidemia³), lifestyle factors (e.g., diet,⁴ obesity,⁵ smoking⁶), medical conditions, and medications. High cholesterol has been cited as a sequela of several diseases such as diabetes,⁷ hypothyroidism,⁸ chronic kidney disease,⁹ liver disease,¹⁰ HIV/AIDS¹¹, and lupus.¹² Medications such as amiodarone,¹³ beta blockers,¹⁴ loop and thiazide diuretics,¹⁵ hormones,^16,17 androgen steroids,¹⁸ corticosteroids,¹⁹ antipsychotics,^20,21 immunosuppressants,²² antivirals,²³ and retinoids²⁴ have also been linked to higher levels of cholesterol. 

According to American College of Cardiology/American Heart Association (ACC/AHA) guidelines, the first and strongest recommended therapeutic modality is lifestyle therapies²⁵, including modifications to diet composition, weight control, and physical activity.¹

Diet

The ACC/AHA recommends that patients follow a healthy eating pattern, encouraging intake of vegetables, fruits, whole grains, legumes, healthy protein sources, and non-tropical vegetable oils while limiting intake of sweets, sugar-sweetened beverages, and red meats (Class of Recommendation [COR] I, Level of Evidence [LOE] A).*⁴ This recommendation is based largely on studies of the Dietary Approaches to Stop Hypertension (DASH) diet and its variations. According to the ACC/AHA analysis of these studies, they have shown that compared to a typical American diet, the DASH diet lowered LDL by about 11 mg/dL while having no effect on triglycerides. This LDL lowering effect was found in adults of all ages and among men, women, African Americans, non-African Americans, hypertensive, and normotensive adults.

Similarly, slight variations on the DASH diet, such as replacing 10% of calories from carbohydrates with protein, also lowered LDL, but more moderately, by about 3 mg/dL, and had a greater effect on triglycerides, lowering by about 16 mg/dL.⁴  Replacing 10% of calories from carbohydrates with unsaturated fat lowered LDL similarly by 3 mg/dL but lowered triglycerides by 10 mg/dL.

They also recommend aiming to only consume 5-6% of daily caloric intake from saturated fat and to reduce intake of saturated and trans-fat in general (COR I, LOE A).⁴ Based on their analysis of studies examining the effect of dietary fat on cholesterol, they found that when adults consumed only 5-6% of their daily caloric intake from saturated fat compared to a control group consuming 14-15% saturated fat, LDL was lowered by about 11-13 mg/dL. In controlled feeding trials, for every 1% of energy from saturated fatty acids (SFA) or trans fats that is replaced by carbohydrates, monounsaturated fatty acids (MUFA), or polyunsaturated fatty acids (PUFA), they found that LDL is lowered.

Table 1. Decrease in serum cholesterol per each 1% of total caloric intake of SFA, carbohydrates, or trans fats replaced with PUFA, MUFA, or carbohydrates (all presented in mg/dL).⁴

The relationship between diets high in dietary cholesterol and subsequent high cholesterol levels is unclear.⁴ Some studies have shown a positive correlative relationship, but many don’t account for the fact that foods high in cholesterol content are also rich in SFA. A 2012-2016 Korea National Health and Nutrition Examination Survey (KNHANES) study that included 39,156 participants found no significant associations between dietary cholesterol intake and TC or LDL levels after controlling for saturated fat intake.²⁶

While high dietary cholesterol alone does not appear to contribute to hypercholesterolemia, because most foods high in cholesterol are more caloric and contain more fat, a diet high in cholesterol can contribute to hyperlipidemia. Additionally, because of cholesterol’s relationship with higher overall calorie and fat intake, diets high in cholesterol can lead to obesity, another secondary cause of hyperlipidemia.⁵

Exercise

A prospective study (n=27,055) of otherwise healthy women estimated that the beneficial effects of physical activity on serum lipid levels accounted for 19% of the observed reduction in cardiovascular disease risk.²⁷

For adults, the ACC/AHA recommends three to four 40-minute sessions of aerobic physical activity each week to reduce LDL and other non-HDL cholesterol (CoR IIa, LoE A).⁴ In studies of physical activity not in combination with any other intervention, aerobic physical activity has been found to reduce LDL by 3-6 mg/dL on average.

Long Term Effects of High Cholesterol

High cholesterol is a risk factor for the development of atherosclerotic cardiovascular disease (ASCVD).¹ Cholesterol contributes to ASCVD progression when the accumulation of cholesterol particles in blood vessel walls causes decreased blood flow through the vessel.

*See ACC/AHA Class of Recommendation and Level of Evidence definitions below: 

References

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