. Sitkiewicz, G. Sygitowicz, G. Sypniewska, T. Tomasik, A. Windak, D. Zozuliska-Zi kiewicz, B. CybulskaTable XXII. Summary of hypertriglyceridaemia management recommendations Variable TG concentration Principal therapy objective Secondary treatment aim Nonpharmacological treatment Mild to moderate elevated VLDL-TG 15085 mg/dl (1.70 mmol/l) Target LDL-C concentration Target non-HDL-C concentration Limited consumption of alcohol or abstinence Weight reduction in case of obesity Reduction of carbohydrate intake, in specific fructose and sucrose Improved physical activity Substitution of saturated fats with unsaturated fats (particularly polyunsaturated) Statin (atorvastatin, rosuvastatin, pitavastatin) Begin with fibrate alone if TG 500 mg/dl (5.6 mmol/l) to lessen the threat of ACS Take into consideration adding PUFA n-3 in case of high cardiovascular threat and TG 150 mg/dl (1.7 mmol/l) Contemplate adding a fibrate in the event the target LDL-C has been achieved and TG 200 mg/dl ( two.3 mmol/l) in main prevention and in high-risk patients HTG primarily polygenic. No indications for genetic testing Serious Chylomicrons and VLDL-TG present 885 mg/dl ( ten mmol/l) TG reduction Target LDL-C and non-HDL-C, when the threat of AP is lowered Alcohol abstinence Restrictive low-fat diet regime (105 of total power) Weight reduction in case of obesity Reduction of total carbohydrate intake, particularly fructose and sucrose Elevated physical activityPharmacological treatmentFibrate (fenofibrate) + PUFA n-3 Volanesorsen in monogenic chylomicronaemia (household chylomicronaemia syndrome, FCS) (nevertheless unavailable in Poland)Genetic testingHTG pretty most likely to be monogenic. Genetic tests indicated in youngsters and adolescents. Encouraged cold flotation test(two two g/day) is used together with eating plan. In monogenic chylomicronaemia, the efficacy of therapy having a fibrate and PUFA n-3 is low, and as pointed out above, successful pharmacotherapy has turn into feasible only recently [215]. It is also worth noting that not too long ago (Could 2019) the EMA has granted conditional approval for the use of a novel agent efficiently lowering TG concentration in monogenic chylomicronaemia [215]. Volanesorsen is an antisense oligonucleotide that Glycopeptide site inhibits translation of apolipoprotein CIII (Apo CIII) mRNA. Apo CIII, present in lipoproteins transporting TG, inhibits lipoprotein lipase (LPL) activity. Volanesorsen is administered subcutaneously when a week for three months, then as soon as every two weeks. It nonetheless has not been approved by the FDA. Thrombocytopenia is often a widespread adverse reaction related with volanesorsen (see section on new agents in remedy of lipid issues) [215]. A sensible summary of management of hypertriglyceridaemia is presented in Table XXII.9.ten. New agents in lipid disorders therapy 9.10.1. Bempedoic acidBempedoic acid is definitely an ATP-citrate lyase (ACL) inhibitor that decreases LDL-C concentrationby means of inhibition of cholesterol synthesis in the liver. ACL is definitely an enzyme preceding 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway [216]. Importantly, bempedoic acid is definitely an inactive prodrug and requires activation by coenzyme A (CoA) with long-chain acyl-CoA 1 synthetase (ACSVL1), and also the complete method requires location Fas Biological Activity inside the liver as an alternative to in skeletal muscles, which in the very beginning indicated that it may be a really successful agent for statin-intolerant individuals [216]. Inhibition of ACL by bempedoic acid decreases hepatic cholesterol synthesis and reduces blood LDL-