Dyslipidemia

Dyslipidemia is a lipid metabolism disorder characterized by the imbalance of lipids such as cholesterol, low-density lipoprotein cholesterol (LDL cholesterol), high-density lipoprotein cholesterol (HDL cholesterol) and triglycerides. The resulting elevated levels of total, LDL cholesterol and triglycerides, or decreased levels of HDL cholesterol, represent one of the major risk factors for the development of atherosclerosis and, subsequently, cardiovascular disease. A distinction is made between primary dyslipidemias, which have genetic causes and result from single or multiple gene mutations (including familial hypercholesterolemia), and secondary dyslipidemias, which occur as a result of disease or the use of medications, as well as lifestyle factors such as diet and smoking. Specific blood parameters are available in the diagnosis of dyslipidemias, including elevated levels of triglycerides and LDL cholesterol. In addition to drug treatment with statins, among others, lifestyle changes play a significant role in the treatment of dyslipidemias. According to the World Health Organization (WHO), cardiovascular diseases are among the leading causes of death, claiming some 17.9 million lives each year and accounting for an estimated 32% of all deaths worldwide.
 

Due to their water-insoluble structure, lipids such as cholesterol or triglycerides are absorbed in the blood from the intestine with the help of so-called apolipoproteins and subsequently transported through the body as lipoproteins (complexes of lipids and proteins) for energy production, bile acid formation and steroid production. Lipoproteins are HDL, LDL, Lp(a) (lipoprotein(a)), VLDL (very-low-density lipoprotein, precursor of LDL), and chylomicrons, which have different functions (including transport of cholesterol and triglycerides). Dyslipidemia is based on an imbalance of one of these factors. The cause of primary dyslipidemias is due to genetics through single or multiple gene mutations. For example, familial hypercholesterolemia is most commonly caused by autosomal dominant mutations in LDL receptors, which subsequently lead to an increase in LDL cholesterol levels. Secondary dyslipidemias (hypercholesterolemia, hypertriglyceridemia and combined hyperlipidemia), on the other hand, arise as a consequence of various diseases, the use of medications, but also certain lifestyle factors (especially malnutrition) can increase lipid levels and exert an influence on the pathogenesis. Here, in addition to a lack of physical activity, alcohol and tobacco consumption, existing obesity and an unbalanced diet, characterized by a high consumption of saturated fatty acids (mainly animal fats, but also, for example, coconut fat) and an insufficient intake of dietary fiber (including fruits, vegetables, nuts and seeds).
 

Due to the frequently asymptomatic course, dyslipidemias often remain undetected for a long time and are usually detected by chance or when cardiovascular complications such as coronary heart disease (CHD), stroke or myocardial infarction already occur. Physical examination in dyslipidemia is limited; however, some skin manifestations including xanthomas and xanthelasmata ("yellow nodules") can be counted among the visible symptoms in hyperlipidemia. These are yellowish deposits of lipids on the skin, which form nodules, plaques and patches and can appear on the hands, feet, knees, eyes (especially the Achilles tendon) or eyelids (xanthelasma palpebrarum). In addition, arcus lipoides corneae (annular lipid deposition in the area of the cornea), steatosis hepatis (fatty liver) and, in the case of hypertriglyceridemia, pancreatitis (inflammation of the pancreas) may also occur.
 

Dyslipidemias can be subdivided according to the Fredrickson classification, which refers to the elevation of lipids and liporoteins. Phenotype I involves an abnormality of chylomicrons leading to an increase in triglycerides. Phenotype IIa consists primarily of an abnormality of LDL cholesterol and results in an increase in total cholesterol. Phenotype IIb involves an abnormality of LDL and VLDL cholesterol, leading to an increase in triglycerides and/or total cholesterol. Phenotype III involves an abnormality of VLDL cholesterol and chylomicron remnants, resulting in elevated total cholesterol and triglycerides. Phenotype IV occurs primarily with abnormality of VLDL and results in elevation of triglycerides. Phenotype V is present with abnormality of chylomicrons and VLDL and results in elevation of triglycerides and total cholesterol.
 

The basis for the diagnosis of dyslipidemia is the determination of total cholesterol and, under certain circumstances, HDL cholesterol in the blood. This can be done in the course of screening examinations or in people with an increased risk due to cardiovascular diseases in the family, or dyslipidemia-associated skin manifestations (see symptoms) and/or factors that promote secondary dyslipidemias. In addition, in those patients who already have primary dyslipidemia, cardiovascular risk, or evidence of dyslipidemia, a so-called lipid profile can be recorded in serum, in which total cholesterol, HDL cholesterol, and triglycerides are measured and LDL and VLDL cholesterol are calculated. In addition, several calculators are now available, including those of the American College of Cardiology and the American Heart Association (ACC/AHA), which were developed to estimate the risk of atherosclerotic cardiovascular disease. This takes into account age, gender, blood pressure, total cholesterol, HDL and LDL cholesterol, diabetes, smoking, hypertension therapy, and statin and aspirin use. The risk of occurrence of a cardiovascular event is determined as a percentage over a 10-year period.  
 

Therapeutic goals in dyslipidemias primarily include maintaining or lowering lipid levels and thereby reducing cardiovascular risk, as well as preventing further complications attributable to this disease. Cardiovascular disease is among the most common complications of dyslipidemia, including acute myocardial infarction, sudden cardiac death, and stroke. In this context, several studies have shown that statin therapy significantly reduces the risk of cardiovascular events and cardiovascular mortality as well as all-cause mortality. Lifestyle modifications play a major role in the prevention and treatment of dyslipidemia. The most important of these are weight control, a healthy, balanced diet with a high proportion of fiber-rich fruits and vegetables, as well as nuts, seeds and vegetable oils, regular physical activity and abstinence from tobacco consumption. In this context, the Mediterranean diet should be mentioned in particular, which is characterized by a high proportion of unsaturated fatty acids such as olive oil, a low consumption of meat (especially little red meat), a moderate consumption of yogurt and cheese , as well as abundant regional and seasonal fruits and vegetables, legumes, nuts and predominantly whole grains. Statins are the drugs of choice for drug therapy, but other lipid-lowering drugs can also be used. In cases of very pronounced dyslipidemia, where other therapies are not tolerated or the desired effect fails to materialize, extracorporeal procedures known as lipidapheresis can also be used.  
 

Polyphenols, as contained in pine bark extract pycnogenol^® and grape seedextract, have a high antioxidative protective potential, especially against reactive oxygen and nitrogen species. Due to their antiedematous, vasodilative, antiphlogistic and antioxidative properties, they are used for the therapeutic treatment of cardiovascular diseases. In addition, they prevent arteriosclerosis-promoting events already in the early phase by preventing oxidative vascular damage.

The Omega-3 fatty acids EPA and DHA have an antiaggregatory and vasodilatory effect on the endothelial cells of the vessels and can lower the triglyceride level. They thus make a significant contribution to protection against cardiovascular diseases. In addition, they inhibit the omega-6 metabolism and use the conversion enzymes to build up "good", anti-inflammatory eicosanoids. This reduces the formation of undesirable vasoconstrictive, proaggregatory and inflammatory eicosanoids from arachidonic acid, which explains the therapeutic effect of omega-3 fatty acids in inflammatory diseases and cardiovascular prophylaxis.

Coenzyme Q10 is an important substance in the prevention and treatment of arteriosclerosis due to its strong antioxidant properties. After a myocardial infarction, Q10 substitution shows a significant reduction in reactive radicals and thus a reduction in the risk of further atherothromboses. In cardiological diseases, such as heart failure and ischaemic heart diseases, the Q10 levels in the heart muscle are significantly lowered. This energetic impoverishment of the tissue can be counteracted by regular daily substitution with 60 – 500 mg Q10. In addition, the coenzyme Q10 status is closely associated with the side effects of cholesterol-lowering statins (CSE inhibitors). The muscle weakness that often occurs as a side effect of statin therapy is attributed to the intervention of CSE inhibitors in the biosynthesis of mevalonic acid. This not only interrupts the build-up of cholesterol, but also the self-synthesis of coenzyme Q10.
 

Red mould rice is a traditional food from Asia, which is won by fermentation of rice with the help of the yeast fungus Monascus purpureus. There is scientific evidence for its cholesterol-lowering effect, which can be traced back to the naturally contained Monacolin K, also known as lovastatin, and 8 related substances. The mechanism of action of red rice is based on that of statins: by inhibiting the HMG-CoA reductase, biosynthesis of new cholesterol is prevented and a long-term reduction in cholesterol levels is achieved. Due to the higher affinity of statins to HMG-CoA reductase (a significant reduction in serum cholesterol levels can be measured after only a few days), the effect of red rice is correspondingly lower.
 

Niacin has long been used for intervention in hypercholesterolaemia. Substitution with niacin effectively reduces plasma concentrations of VLDL and LDL, while HDL levels increase.

Proanthocyanidins (OPC) also appear to have a direct effect on the lipid profile in hypercholesterolaemia. In clinical trials the LDL levels in patients with elevated levels could be significantly reduced by an intake of 100 mg grape seedextract over 2 months. In addition, they increase the oxidation resistance of LDL cholesterol to free radicals. Another study showed the cardioprotective effect of 195 mg punicalagin supplementation from pomegranate extract by improving the dyslipidaemia shown in adults. 

Zeolite of different grinds reduces both total and LDL cholesterol and simultaneously leads to a reduction in triglyceride levels and an increase in HDL cholesterol. According to current research, these effects are detectable as long as zeolite is supplemented; as early as six weeks after discontinuation of the supplement, baseline concentrations may be restored and the beneficial effect may be nullified. The fineness of the zeolite powder also has a strong effect on the results: The finer the zeolite powder, the stronger the effects on the lipid profile and the longer the effect lasts.