DISORDERS OF LIPID METABOLISM Dyslipidemias Dyslipidemia in the Czech population 0 20 40 60 80 100 25- 34 35- 44 45- 54 55- 64 0 20 40 60 80 100 25- 34 35- 44 45- 54 55 - 64 M W Age % % TC > 5.0 or HDL-ch. < 1.0 or LDL-ch. > 3.0 or TG > 2 mmol/l or treatment with hypolidemic drugs Age Mechanism of DLP development Environment effects Other diseases effects Genetic effects DLP Cholesterol as a risc factor of AS * CHD: Yes * PAD: ?? * Stroke: Ano * Carotid art.: Yes Physiologic levels of blood lipids - ,,healthy" population, ,,primary" prevention * Total cholesterol < 5.0 mmol/l * LDL cholesterol < 3.0 mmol/l * Triglycerides < 1.7 mmol/l * HDL cholesterol > 1.0 mmol/l * Regardless of age and sex Goal levels of blood lipids for high risk patients * Total chol. < 4,5 mmol/l * LDL chol. < 2,5 mmol/l * HDL chol. (men) > 1.0 mmol/l * HDL chol. (women) > 1.2 mmol/l * Triglycerides: < 1.7 mmol/l Goal levels of blood lipids for very high risk patients * Total chol. < 4,5 mmol/l * LDL chol. < 2,0 mmol/l 4 < 1,8 mmol/l * HDL chol. (men) > 1.0 mmol/l * HDL chol. (women) > 1.2 mmol/l * Triglycerides: < 1.7 mmol/l Therapeutic classification of DLP * Hypercholesterolemia * Hypertriglyceridemia * Mix hyperlipidemia * Primary (inherent) DLP * Secondary DLP Secondary DLP * Subject to endocrine diseases * Liver diseases * Kidney diseases * Drugs-induced DLP * Toxonutritive DLP * DLP induced by environmental influences DLP due to endocrine diseases * Diabetes mellitus 4Undercontrolled * Hypothyreosis * Hyperfunction of suprarenal glands 4Cushing disease * Pregnancy (physiological DLP) ˇ Cholestasis 4Primary biliary cirrhosis * Parenchyma liver disease 4Hepatitis (no steatosis) DLP due to hepatic diseases ˇ Nephrotic syndrome * Chronic renal insufficiency 4Haemodialysis, peritoneal dialysis * Renal transplantation DLP due to renal diseases Drugs-induced DLP * Antihypertenzive drugs 4High doses of Thiazid diuretics, non-selective -blockers * Immunosuppressive 4Cyclosporine A 4Corticosteroides Toxonutritive DLPs: alcohol * Alcohol increases blood lipids !!! * This effect is dose-dependent 4 Individual sensitivity to the alcohol * This type of DLP is not atherogenic * Leading cause of secondary DLP resistant to the therapy DLPs induced by the environment influences * Food 4High intake of saturated fats, glucose, cholesterol 4Genetic disposition * Smoking 4 HDL-Ch * Physical inactivity 4 HDL-Ch, Tg Primary DLP (genetic DLP) * Hypercholesterolemia 4Familial hypercholesterolemia 4Polygenic HCH * Hypertriglyceridemia 4Familial HTg * Mix DLP 4Familial combined DLP Familial hypercholesterolemia * Cause 4Defective LDL-receptor gene 4Defective apo B gene * Frequency: 1: 500 (heterozygote type) * Heredity: autosomal dominant * Patophysiology: catabolism of LDL particles is very slow * Laboratory: Chol. 9-15 mmol/l 4 Physiologic level of Tg, HDL-ch) * Premature CHD * Xantomatosis is relative rare Familial hypertriglyceridemia * Cause: ?? 4Interaction of several genes (apo C, LPL, B) 4Environment influence * Frequency: 1:300 * Heredity: autosomal dominant * Patophysiology: synthesis, catabolism of VLDL particles * Laboratory: Tg > 3 mmol/l (Ch: ), HDL-C Familial combined HLP * Cause: not known 4Interaction of several genes (apo B, C, E, LPL) 4Environment influence * Frequency: 1:100 * Heredity: autosomal dominant * Patophysiology 4 synthesis of apo B a Tg 4 catabol. of VLDL, LDL * Laboratory: Tg, Ch (LDL-Ch), apo B * Premature CHD Polygenic hypercholesterolemia * Cause: not known 4Interaction of several genes (apo B, E) 4Environment influence * Frequency: 1:100-200 * Patophysiology: synthesis, catabol. of LDL * Laboratory: Chol 6 - 8 mmol/l (Tg = N) * Premature CHD Non-pharmacology treatment * Stop smoking !!! * Physical activity, exercise * Weight lose 4In case of overweight or obesity * Diet Pharmacotherapy of DLP * Only if CHD risk is high 4Patients with CHD, or CHD equivalent 4Patients with diabetes mellitus 4Patients with familial hypercholesterolemia * Other peoples 4Only if other risk factors are present Age (> 45 men, > 55 women) Smoking, hypertension Pharmacotherapy of DLP Fibrates Nicotinic acid Decrease of triglycerides Elevation fo HDL cholesterol Statins Ezetimibe Resins Decrease of LDL cholesterol