As lipid metabolism disorders are steadily gaining strength today, their increase makes us look for ways to correct the pathology. These include cholesterol reduction, and balancing the diet with control of eating behavior by controlling leptin and other fat cell hormones. You will learn more about the principles of treating lipid metabolism disorders in this article.
- Reducing cholesterol.
- Diet Therapy.
- Reason for prescribing statins.
- Nicotinic acid.
- Other drugs.
One of the most effective ways to correct lipid metabolism disorders is to lower the total cholesterol to a normal level and prevent its possible increase in the future. Moreover, we are talking not only about the correction of total cholesterol, but also about one of its fractions – low density lipoproteins (LDL). But does this balancing guarantee active longevity? Does it improve quality of life? Let’s take the CARE study as an example.
In the experiment it was proved that minimization of low-density cholesterol levels below 3.2 mmol/l does not worsen the situation and is not life-threatening. But at the same time, the POST-CABGT study, which included patients after aortocoronary bypass surgery, proved the lack of need for repeated interventions in 30% of cases if LDL levels were reduced to 2.6 mmol/L (comparison was made with lipid levels of 3.4-3.5 mmol/L).
Approximately the same data were obtained in the CARS study, which focused on patients with CHD. They took a group with relatively normal total cholesterol (4.1 to 5.6 mmol/L) and a group with average low-density lipid levels (3.17 mmol/L). thus, today we can consider that minimizing cholesterol levels is the goal of therapy in the secondary prevention of CHD. In the EU, this goal is considered to be less than 3.0 mmol/L for LDL, and in the United States, less than 2.6 mmol/L.
There are two main ways to achieve this goal: medications and diet. But any correction should start with the elimination of risk factors that contribute to the development of atherosclerosis: smoking, alcohol, stress, sedentary lifestyle. Plus, BMI balancing involving leptin. In case of disorders of fat metabolism, which develop against the background of hypothyroidism, nephrosis, metabolic syndrome – first of all, the root cause of the pathology should be eliminated.
Leptin-affiliated nutritional correction is one of the main methods of non-drug therapy. Its essence is the restriction of fats of animal origin and easily absorbable carbohydrates, minimizing the caloric content of the diet. There is data from an experiment from Veterans Administrations where patients were prescribed a diet with an increased content of polyunsaturated fatty acids and a minimum of animal fats compared to patients who practiced the standard North American diet.
This dietary pattern over 8 years resulted in a drop in total cholesterol levels of almost 13%, and reduced the incidence of myocardial infarctions by 20%. At the same time, there was no reduction in overall mortality in any of the patient groups observed.
In the Finnish Mental Hospital Study, a low-cholesterol diet reduced cholesterol levels by 15% over 6 years in nearly 500 patients of both sexes aged 35+ to 65 years. At the same time, achieving an average total cholesterol level (5.8 mmol/L) did not cause a significant reduction in overall mortality or cardiovascular mortality.
In the DART study, which included more than 2000 patients aged 55+, adherence to the diet for a couple of years did not significantly reduce overall mortality or mortality from CHD. However, nonfatal ischemia was even more common in the group of patients who followed the diet.
The largest study, the Minnesota Coronary Survey, which included about 5,000 patients of either sex and any age with a baseline total cholesterol level of 5.3 mmol/L, showed that the hypocholesterol diet alone gave a minimization of total cholesterol levels of almost 15% compared with the control group. This study showed no drop in cardiovascular abnormalities and no minimization of overall mortality.
Thus, it turns out that therapy of patients with hypercholesterolemia and hypertriglyceridemia should begin with elimination of risk factors and root causes of the pathology, and only then – with a hypocholesterol diet. If a diet is effective, it can be considered the only way to correct it only if the patient is able to stick to it for the rest of his/her life.
But here also the patients with CHD during exacerbation of the pathology and in case of severe hypercholesterolemia, along with keeping to a diet, simultaneously prescribe hypocholesterolemic preparations in individual doses. Normalization of fat metabolism indices by diet alone is impossible, and untimely initiation of therapy leads to the development of serious complications.
In the absence of acute momentum and non-drug therapy for a maximum of three months, drug correction is connected. Hypolipidemic drugs of any class do not mean refusal of diet; on the contrary, such therapy becomes only more effective against the background of diet.
Today, five main classes of drugs are used, which act according to the presence of side effects, contraindications, and effectiveness in a particular type of fat metabolism disorders.
The main class are statins, but in addition to them work:
- nicotinic acid;
- bile acid sequestrants;
We emphasize that, at present, the effect on overall mortality, the development of complications from cardiovascular diseases, mortality from them has been proven only for statins. Their mechanism of action is based on the inhibition of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-co-A)-reductase. Cholesterol synthesis is blocked in the liver and intestines, and statins minimize intracellular stores of the substance.
This causes formation of increased number of receptors to low density lipoproteins and stimulates their removal from plasma. There is information about the effect of statins on platelet aggregation and vascular endothelium, but this mechanism is not fully understood.
The effect of statins is to reduce the concentration of low-density lipids and total cholesterol. High doses of statins significantly minimize triglyceride levels, which allows them to compete with fibrates.
A 10-mg dose of Simvastatin is considered to be roughly equal to 20 mg of Lovastatin or Pravastatin and 40 mg of Fluvastatin. Doubling the dose of statins relative to the original dose further reduces total cholesterol by 5 and LDL by 7%. At the same time the increase in cholesterol concentration does not correlate with the dose of the drug. Statins are used for the prevention of CHD, both primary and secondary (in patients with proven CHD).
Reason for prescribing statins
The efficacy of statin prescribing is correlated not only with the level of baseline fat metabolism. The cumulative risk of cardiovascular complications and the disease clinic plays a major role. For example, in patients with acute coronary syndrome, the therapeutic effect of statins is more pronounced than in patients with stable angina pectoris, with more aggressive tactics. Statins, like Aspirin and β-blockers, directly affect the prognosis of pathology in patients with CHD. Statins have also been proven to be effective for prophylactic purposes.
Numerous studies confirm the efficacy of statin treatment and prevention of CHD. At the same time, the prescription of statins in secondary prevention is more pronounced and more economically justified. This means that statins in patients with diagnosed CHD combined with lipid metabolism disorder are used in all patients. The efficacy of drugs of this group in patients with severe dyslipidemia is higher.
The development of coronary insufficiency in patients with CHD against the background of normal parameters of fat metabolism indicates the multifactorial genesis of complications and focuses not only on the level of metabolic disorders, but also on a complex of factors, the main of which is considered to be the symptomatology of pathology exacerbation.
One of the serious triggers of the efficacy of hypocholesterolemic drugs in the prevention of CHD is considered to be their ability to inhibit the progression or stimulate the regression of atherosclerosis. These effects have been confirmed by measuring vascular diameter arteriographically or by intravascular ultrasound. The MAAS study in patients with CHD suggests that Simvastatin therapy at a dose of 20 mg for four years significantly reduced the development of new coronary stenoses and regression of existing ones by more than 50%.
Inhibition of pathology progress or regression of atherosclerosis is achieved by intensive hypocholesterolemic therapy with significant minimization of LDL concentration. Simvastatin and Atorvastatin in similar doses have the greatest hypocholesterolemic activity.
According to SMAC data, the use of drugs in dose 10-20 mg per day gives the possibility to reach the target level for one and a half year of treatment in half of patients with CHD and a baseline level of low-density lipoproteins from 4.2 to 7.8 mmol/l. At the same time the effect of Atorvastatin came a little earlier, after 4 months there was already an effect in almost half of the patients, whereas with Simvostatin – only in 30%.
By the end of the year the difference had leveled off. This proved the pronounced hypocholesterolemic activity of both drugs and approximately the same effect after one year. At the same time, the cost of Simvastatin is lower than Atorvastatin, which is worth considering.
Another important hypolipidemic medication used to balance fat metabolism is nicotinic acid and its derivatives (niacin). The advantage of this substance is that it works without error. Along with minimizing the concentration of total cholesterol and low-density proteins, triglyceride concentrations are reduced and HDL levels are successfully increased.
In addition, these drugs have other benefits:
- Reduce levels of lipoprotein “a,” which itself is a risk factor for heart attack or stroke.
- Minimize LDL levels by affecting the smallest, most atherogenic particles of LDL.
- Increase the concentration of HDL due to the HDL2 fraction, which is considered to be the most active in terms of removing lipids from plaques, thus blocking the progression of atherosclerosis.
Thus, minimizing the risk of cardiovascular complications, total mortality, if Nianacin is used. A number of drugs were compared in the States, and it seemed that in men 30 to 65 years old who had had at least one heart attack, nicotinic acid was the only drug that could minimize nonfatal heart attacks by about a third and strokes by a quarter. The number of hospitalizations for cardiovascular complications dropped by 12% and the need for surgical intervention by almost 50%. Unfortunately, there were no reliable data on mortality reduction.
A serious advantage of the nicotinic acid products is their low cost. The slow-release forms of nicotinic acid that provide a prolonged and gradual release of the active compound, which minimizes side effects, are in the greatest demand today.
Such medications include:
- combination of nicotinic acid and polygel;
- capsule nicotinic acid with an inert filler;
- nicotinic acid in a tropical wax matrix (Enduracin).
The efficacy of the drugs of the group is slightly different: the bioavailability of prolonged-acting Niacin with a wax matrix is twice as high as with a dosed release. From this, the efficacy of Enduracin at a dose of 1500 mg per day in relation to both high and low density lipoproteins is even slightly greater than when taking 3000 mg of Niacin with prolonged release.
The maximum daily dose of nicotinic acid preparations does not exceed 6 g, and for enduracin – 3 g. A common feature of all drugs of this group is the need to slowly increase the dose under control of fat metabolism parameters, even taking into account good tolerability.
Therapy starts with 500 mg per day for a week, then the frequency is increased to two times, after three weeks the dose is adjusted according to the lipid metabolism indices. To minimize side effects, the medication is taken with meals, and small doses of Aspirin (100-325 mg) are added for symptoms of hyperemia. This reduces the symptoms for the first three days until they completely disappear later.
Side effects include hot flashes and skin itching, plus hyperesthesia and parasthesias, dyspepsia, constipation, tachycardia, vertigo, ataxia, dry dermis, and skin pigmentation disorders. Such adverse manifestations do not exceed 7%. Biochemical tests are performed monthly to monitor for adverse liver complications. Nausea or other negative symptoms require withdrawal of the drug, analysis for liver tests. Blood sugar and uric acid are necessarily tested.
The use of drugs from other drug groups – fibrates, bile acid sequestrants and antioxidants – also provide an opportunity to improve fat metabolism. But even today there are no data on their impact on overall mortality, fatal outcomes from cardiovascular pathologies, cardiac complications, the frequency of hospitalizations and surgical interventions.