Atherogenic Dyslipidemia (AD)

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Atherogenic dyslipidemia (AD) is a clinical disorder that, in my opinion, is far too often overlooked.  It depicts a blood lipid pattern characterized by elevated triglycerides (TG) and low levels of high-density lipoprotein cholesterol (HDL-C). Hence, people with AD have an elevated TG/HDL-C ratio (1).

More crucially, individuals with AD have elevated apolipoprotein B (apoB) levels and their amount of small low-density lipoprotein (LDL) particles is increased,

AD is a common clinical disorder, mostly due to the rapidly increasing prevalence of abdominal obesity and metabolic syndrome.

On top of that, a considerable proportion of patients at risk of coronary events in routine clinical practice have AD. Studies suggest that AD may be present in up to 40% of patients with coronary artery disease (CAD) (2).

Studies show that AD is associated with an increased risk of developing CAD as well as an increased risk of new events in patients who already have established heart disease (3,4).

Unfortunately, AD often tends to be overshadowed by the huge emphasis on modifying low-density lipoprotein cholesterol (LDL-C). However, many individuals with normal LDL-C develop CAD. A large proportion of these patients may have AD.

Diet is the cornerstone of treatment in patients with AD. Evidence suggests that carbohydrate restriction may effectively improve many of the metabolic abnormalities associated with the disorder.

Atherogenic Dyslipidemia is Associated with Other Important Metabolic Abnormalities

Patients with AD frequently have other lipid abnormalities that may help to explain why their risk of atherosclerotic cardiovascular disease is increased.

Above all, ApoB is usually elevated. ApoB is a marker of the amount of all atherogenic lipoprotein particles and is highly associated with the risk of developing CAD (5).

Increased presence of small LDL particles is typically found in people with AD. Studies show that the number of small, dense LDL particles  may predict the risk for CAD (6). 

Interestingly, the TG/HDL-C ratio may be a valuable predictor of the number of small LDL particles (7).

Altered metabolism of TG-rich lipoproteins is believed to play a key role in AD. There is overproduction and impaired clearance of VLDL from the circulation. There is also slower clearance of chylomicrons derived from the intestines. Hence, increased remnant lipoproteins are often present in high amounts in patients with AD(8). 

Remnant lipoproteins, such as very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), may contribute importantly to the risk of atherosclerotic heart disease in patients with AD (9). These remnant lipoproteins typically contain large amounts of TG as well as cholesterol (remnant cholesterol).

When triglycerides are released from VLDL, its composition changes and it becomes IDL. Subsequently, the amount of cholesterol increases and IDL becomes LDL. It is now commonly accepted that small, dense LDL particles are the products of remodeling of TG-rich VLDL particles (10).

In summary, high levels of ApoB, large amounts of small, dense LDL particles, and high levels of TG- and cholesterol-rich remnant lipoproteins may all help to explain why patients with AD are at increased risk of heart disease.

AD is characteristically found in patients with abdominal obesity, metabolic syndrome, and type-2 diabetes (11) Insulin resistance is a common nominator for these disorders. Thus, it is no surprise that AD is sometimes referred to as the dyslipidemia of insulin resistance (12).

Studies indicate that AD is associated with elevated levels of hs-CRP, suggesting continuous low-grade inflammation (13,14). Inflammation plays a major role in the initiation and progression of atherosclerosis.

The Dietary Approach to Atherogenic Dyslipidemia 

A very important question is whether and how different diets may improve or worsen the lipid abnormalities associated with AD.

When it comes to the classical question between carbohydrates and fats, there is certainly a lot of evidence suggesting that added sugar and refined carbohydrates are the main drivers of AD (15). High consumption of sugar and refined carbohydrates will promote VLDL production by the liver, a phenomenon, known as carbohydrate-induced hypertriglyceridemia (16). Hence, a high carbohydrate diet may further promote atherogenic dyslipidemia.

Dietary fat, on the other hand, is not a significant source of increased TG-rich lipoproteins and high-fat diets usually don’t raise fasting TG (18).

One study found that moderate carbohydrate restriction and weight loss both improved the lipid abnormalities associated with AD (19).

Another study found that substituting protein for carbohydrate decreased plasma TG in a manner that was independent of saturated fat intake but that reductions in other lipoprotein-related risk factors, including apoB and small LDL, were greatest following consumption of a low-carb-low-saturated-fat diet (20).

Evidence shows that low-fat and low-carbohydrate diets can both be used to induce weight loss. Low- and very low-carbohydrate diets are more effective for short-term weight loss than low-fat diets, although the long-term difference between these two approaches appears similar (21).