Niacin is considered to be a powerful drug for the treatment of lipid and lipoprotein abnormalities connected with "residual cardiovascular risk", which persist in high-risk patients even when the target goals of LDL-C are achieved with statin therapy. Recent large randomized clinical studies - AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides) and HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) - delivered some disappointing results, leading to the conclusion that no further benefit (decreased parameters of cardiovascular risk) is achieved by adding niacin to existing statin therapy in patients with high cardiovascular risk. Moreover, in these studies, several adverse effects of the treatment were observed; therefore, niacin treatment for hypolipidemias is not recommended. In this paper, we analyze the mechanisms underlying the hypolipidemic and antiatherogenic effects of niacin as well as some limitations of the designs of the AIM HIGH and HP2-THRIVE studies. We also provide the possibilities of rational usage of niacin for specific types of dyslipidemias.

• MeSH
• hyperlipidemie farmakoterapie   MeSH
• hypolipidemika škodlivé účinky   terapeutické užití   MeSH
• kardiovaskulární nemoci krev   farmakoterapie   MeSH
• lidé MeSH
• niacin škodlivé účinky   terapeutické užití   MeSH
• rizikové faktory MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• hypolipidemika MeSH
• niacin MeSH

Despite intensive preventive cardiovascular disease (CVD) efforts, substantial residual CVD risk remains even for individuals receiving all guideline-recommended interventions. Niacin is an essential micronutrient fortified in food staples, but its role in CVD is not well understood. In this study, untargeted metabolomics analysis of fasting plasma from stable cardiac patients in a prospective discovery cohort (n = 1,162 total, n = 422 females) suggested that niacin metabolism was associated with incident major adverse cardiovascular events (MACE). Serum levels of the terminal metabolites of excess niacin, N1-methyl-2-pyridone-5-carboxamide (2PY) and N1-methyl-4-pyridone-3-carboxamide (4PY), were associated with increased 3-year MACE risk in two validation cohorts (US n = 2,331 total, n = 774 females; European n = 832 total, n = 249 females) (adjusted hazard ratio (HR) (95% confidence interval) for 2PY: 1.64 (1.10-2.42) and 2.02 (1.29-3.18), respectively; for 4PY: 1.89 (1.26-2.84) and 1.99 (1.26-3.14), respectively). Phenome-wide association analysis of the genetic variant rs10496731, which was significantly associated with both 2PY and 4PY levels, revealed an association of this variant with levels of soluble vascular adhesion molecule 1 (sVCAM-1). Further meta-analysis confirmed association of rs10496731 with sVCAM-1 (n = 106,000 total, n = 53,075 females, P = 3.6 × 10-18). Moreover, sVCAM-1 levels were significantly correlated with both 2PY and 4PY in a validation cohort (n = 974 total, n = 333 females) (2PY: rho = 0.13, P = 7.7 × 10-5; 4PY: rho = 0.18, P = 1.1 × 10-8). Lastly, treatment with physiological levels of 4PY, but not its structural isomer 2PY, induced expression of VCAM-1 and leukocyte adherence to vascular endothelium in mice. Collectively, these results indicate that the terminal breakdown products of excess niacin, 2PY and 4PY, are both associated with residual CVD risk. They also suggest an inflammation-dependent mechanism underlying the clinical association between 4PY and MACE.

• MeSH
• kardiovaskulární nemoci * MeSH
• lidé MeSH
• myši MeSH
• niacin * MeSH
• proporcionální rizikové modely MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Názvy látek
• niacin * MeSH

Hyperlipidemia treatment based on niacin requires gastrointestinal administration of relatively high doses. The recommended dietary allowance of niacin as vitamin B3 is 14 to 16 mg daily in adults, while the doses of niacin used in the treatment of hyperlipidemia are generally in the range of 1 to 3 g. Administration of such large doses requires a high concentration of the active compound in the tablet and proper control of the drug release. In this study, a hydrogel matrix based on poly(2-hydroxyethyl methacrylate) and polyvinylpyrrolidone was investigated as delivery vehicle for controlled NA release into the gastrointestinal environment. The prepared hydrogel matrices varied in used monomer and crosslinker types and concentrations. The content of NA in tablets was between 65-80 %. The release profiles of NA from tablets were examined under three different pH values (1, 4.5 and 6.8) over the time period of 30 h. The effects of the monomer ratio, the crosslinking of the polymer network, and the solubility of niacin during drug release under various pH are discussed. The results showed that the release time period can be achieved in a relatively wide range of time and can be adjusted according to the medical requirements.

• MeSH
• gastrointestinální trakt * MeSH
• hydrogely MeSH
• hyperlipidemie farmakoterapie   MeSH
• hypolipidemika aplikace a dávkování   terapeutické užití   MeSH
• léky s prodlouženým účinkem MeSH
• methakryláty MeSH
• niacin aplikace a dávkování   terapeutické užití   MeSH
• nosiče léků MeSH
• povidon MeSH
• reagencia zkříženě vázaná MeSH
• rozpustnost MeSH
• systémy cílené aplikace léků MeSH
• tablety MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hydrogely MeSH
• hydroxyethyl methacrylate MeSH Prohlížeč
• hypolipidemika MeSH
• léky s prodlouženým účinkem MeSH
• methakryláty MeSH
• niacin MeSH
• nosiče léků MeSH
• povidon MeSH
• reagencia zkříženě vázaná MeSH
• tablety MeSH

• Klíčová slova
• BLOOD *, NICOTINIC ACID/in blood *, SPECTROPHOTOMETRY *,
• MeSH
• fotometrie * MeSH
• krev * MeSH
• kyseliny nikotinové * MeSH
• lidé MeSH
• niacin krev   MeSH
• spektrofotometrie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyseliny nikotinové * MeSH
• niacin MeSH

In human organism, the administration of nicotinic acid (niacin) leads to two types of effects. Within the physiological range (approximately = 20 mg/day), niacin has a vitamin-like role as pellagra preventing factor. The pharmacological dosage (approximately 0,5-4,5 g/day) substantially influences the plasma lipid and lipoprotein concentrations: decreases VLDL and LDL concentrations, changes the profile of LDL subfractions towards the larger particles as well as particles with lower density; it also profoundly increases the concentration of HDL-C in consequence of elevated concentration of HDL2 subfraction. Niacin as the only hypolipidemic drug reduces the lipoprotein(a) concentration. The hypolipidemic mechanism of niacin is different from that of other hypolipidemic drugs. On the basis of clinically controlled trials (both interventional epidemiological and angiographical), which satisfy the criteria of evidence-based medicine, it is possible to conclude that niacin falls unambiguously into the class of hypolipidemic drugs with proven beneficial effect not only on cardiovascular mortality and morbidity, but also on total mortality. Therefore, niacin should have an indisputable role in the pharmacological control of dyslipidemias. With the respect of basic mechanism (inhibition of the lipolysis of adipose tissue) with subsequent decrease in the concentration of free fatty acids and their flux to liver, niacin fulfils the criteria for pathogenetic treatment of atherogenic dyslipidemia in metabolic syndrome. The prerequisite condition for the niacin treatment is the respect for serious adverse effects and possible health hazards of administration (skin flush, hepatotoxicity and deterioration of glucose homeostasis). Recently discovered extrahypolipidemic effects of niacin (antioxidative activity, facilitation of reverse cholesterol transport, activation of PPAR-gamma, antithrombotic effects) and the introduction of drug forms with sustained (extended resp.) release of active compound (that minimizes the adverse effects and administration hazards) form together the basis for firm statement that the derivatives of nicotinic acid should be introduced to the clinical practice in Czech Republic.

• MeSH
• hyperlipidemie farmakoterapie   MeSH
• hypolipidemika farmakologie   terapeutické užití   MeSH
• lidé MeSH
• niacin škodlivé účinky   farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• hypolipidemika MeSH
• niacin MeSH

Hypertriglyceridemia is an important marker of increased levels of highly atherogenic remnant-like particles. The importance of lowering plasma levels of triglycerides (TG) has been called into question many times, but currently it is considered an integral part of residual cardiovascular risk reduction strategies. Lifestyle changes (improved diet and increased physical activity) are effective TG lowering measures. Pharmacological treatment usually starts with statins, although associated TG reductions are typically modest. Fibrates are currently the drugs of choice for hyperTG, frequently in combination with statins. Niacin and omega-3 fatty acids improve control of triglyceride levels when the above measures are inadequately effective. Some novel therapies including anti-sense oligonucleotides and inhibitors of microsomal triglyceride transfer protein have shown significant TG lowering efficacy. The current approach to the management of hypertriglyceridemia is based on lifestyle changes and, usually, drug combinations (statin and fibrate and/or omega-3 fatty acids or niacin).

• MeSH
• chování snižující riziko * MeSH
• hypertriglyceridemie krev   terapie   MeSH
• hypolipidemika terapeutické užití   MeSH
• kyseliny mastné omega-3 terapeutické užití   MeSH
• lidé MeSH
• niacin terapeutické užití   MeSH
• randomizované kontrolované studie jako téma metody   MeSH
• rizikové faktory MeSH
• statiny terapeutické užití   MeSH
• triglyceridy krev   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• hypolipidemika MeSH
• kyseliny mastné omega-3 MeSH
• niacin MeSH
• statiny MeSH
• triglyceridy MeSH

• Klíčová slova
• NICOTINIC ACID ISOMERS *,
• MeSH
• isomerie * MeSH
• isoniazid * MeSH
• kyseliny nikotinové * MeSH
• niacin * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• isoniazid * MeSH
• kyseliny nikotinové * MeSH
• niacin * MeSH

• Klíčová slova
• DIURESIS/pharmacology *, NICOTINIC ACID/pharmacology *,
• MeSH
• diuréza farmakologie   MeSH
• kyseliny nikotinové * MeSH
• niacin farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyseliny nikotinové * MeSH
• niacin MeSH

• Klíčová slova
• NICOTINIC ACID ISOMERS/therapeutic use *, TUBERCULOSIS/therapy *,
• MeSH
• isomerie * MeSH
• isoniazid * MeSH
• kyseliny nikotinové terapeutické užití   MeSH
• niacin * MeSH
• tuberkulóza terapie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• isoniazid * MeSH
• kyseliny nikotinové MeSH
• niacin * MeSH

• Klíčová slova
• NICOTINIC ACID *, RETINA *,
• MeSH
• kyseliny nikotinové * MeSH
• niacin * MeSH
• retina * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyseliny nikotinové * MeSH
• niacin * MeSH