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niacin and lipoprotein a

Priska Stahel, Changting Xiao, Robert A Hegele, Gary F Lewis
Despite the effectiveness of low-density lipoprotein (LDL)-lowering strategies for the treatment of diabetic dyslipidemia, significant residual risk of atherosclerotic cardiovascular disease remains. Residual risk might in part be explained by lipid abnormalities that go beyond LDL cholesterol elevation, collectively termed the "atherogenic dyslipidemia complex (ADC)," consisting of hypertriglyceridemia, elevated small dense LDL particles, reduced high-density lipoprotein cholesterol, and high-density lipoprotein particle numbers, increased remnant lipoproteins, and postprandial hyperlipidemia...
December 15, 2017: Canadian Journal of Cardiology
Sarah Parish, Jemma C Hopewell, Michael R Hill, Santica Marcovina, Elsa Valdes-Marquez, Richard Haynes, Alison Offer, Terje R Pedersen, Colin Baigent, Rory Collins, Martin Landray, Jane Armitage
BACKGROUND: Genetic studies have shown lipoprotein(a) (Lp[a]) to be an important causal risk factor for coronary disease. Apolipoprotein(a) isoform size is the chief determinant of Lp(a) levels, but its impact on the benefits of therapies that lower Lp(a) remains unclear. METHODS: HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is a randomized trial of niacin-laropiprant versus placebo on a background of simvastatin therapy...
February 2018: Circ Genom Precis Med
Xinran Wang, Wei Li, Lijuan Hao, Honglei Xie, Chenzhou Hao, Chunchi Liu, Wenyan Li, Xuqiong Xiong, Dongmei Zhao
Epidemiological studies have identified that high levels of low-density lipoprotein-cholesterol (LDL-C) and low levels of high-density lipoprotein-cholesterol (HDL-C) are two independent causes of cardiovascular disease (CVD). Statins, niacin and fibrate are used for the treatment of CVD. However, some defects are shown in the treatment process. Thus, there is a demand for better treatment strategies that confer preferable efficacy with fewer side effects. Cholesteryl ester transfer protein (CETP) promotes the movement of CEs from HDL to LDL and VLDL in exchange for triglycerides (TGs)...
February 9, 2018: Expert Opinion on Therapeutic Patents
James D Otvos, John R Guyton, Margery A Connelly, Sydney Akapame, Vera Bittner, Steven L Kopecky, Megan Lacy, Santica M Marcovina, Joseph B Muhlestein, William E Boden
BACKGROUND: The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial showed no incremental benefit of extended-release niacin (ERN) therapy added to simvastatin in subjects with cardiovascular disease (CVD). OBJECTIVES: To examine the effects of ERN treatment on lipoprotein particles and GlycA, a new marker of systemic inflammation, and their relations with incident CVD events including mortality...
January 12, 2018: Journal of Clinical Lipidology
Michael Zimmer, Pradeep Bista, Ericka L Benson, Diana Y Lee, Feng Liu, Dominic Picarella, Rick B Vega, Chi B Vu, Maisy Yeager, Min Ding, Guosheng Liang, Jay D Horton, Robert Kleemann, Teake Kooistra, Martine C Morrison, Peter Y Wielinga, Jill C Milne, Michael R Jirousek, Andrew J Nichols
CAT-2003 is a novel conjugate of eicosapentaenoic acid (EPA) and niacin designed to be hydrolyzed by fatty acid amide hydrolase to release EPA inside cells at the endoplasmic reticulum. In cultured liver cells, CAT-2003 blocked the maturation of sterol regulatory element-binding protein (SREBP)-1 and SREBP-2 proteins and decreased the expression of multiple SREBP target genes, including HMGCR and PCSK9 . Consistent with proprotein convertase subtilisin/kexin type 9 (PCSK9) reduction, both low-density lipoprotein receptor protein at the cell surface and low-density lipoprotein particle uptake were increased...
June 2017: Hepatology communications
Fan Wang, Xiaona Wang, Ping Ye, Ruihua Cao, Yun Zhang, Yue Qi, Dong Zhao
BACKGROUND: Although drug trials with niacin and cholesteryl ester transfer protein inhibitors that substantially increase high-density lipoprotein-cholesterol (HDL-C) failed to reduce the risk of coronary heart disease, HDL protection of the cardiovascular system cannot be easily denied. Hence, it may be HDL subfractions that are responsible for the long-held and consistent cardioprotective association of HDL. Arterial stiffness has been increasingly recognized as a strong predictor of subclinical vascular disease, atherosclerotic disease, and cardiovascular mortality...
January 5, 2018: Lipids in Health and Disease
Ji Yoon Han, Hyun Jeong Kim, Soyoung Shin, Joonhong Park, In Goo Lee
RATIONALE: Stroke is an uncommon disease in childhood with an estimated incidence of 1 to 6 per 100,000 and stenoocclusive arteriopathy is the main risk factor of recurrent pediatric arterial ischemic stroke (AIS). Dyslipidemia may influence strongly before puberty and in late adolescence when plasma levels are naturally highest. PATIENT CONCERNS: An 11-year-old male presented with acute onset seizure, a drowsy mentality, and right hemiplegia. DIAGNOSES: Magnetic resonance (MR) angiogram demonstrated occlusion of distal basilar artery and left vertebral arteries...
December 2017: Medicine (Baltimore)
Rabban Mangat, Faye Borthwick, Tina Haase, Miriam Jacome, Randy Nelson, Anatol Kontush, Donna F Vine, Spencer D Proctor
The intestine is involved in whole-body lipid and cholesterol homeostasis and secretes lipoproteins containing apolipoprotein (Apo)B48 and discrete ApoA-I into the mesenteric lymph. The lymphatic system has been proposed to have a significant role in the reverse cholesterol transport pathway associated with HDL-ApoA-I. In conditions of insulin resistance (IR), there is intestinal overproduction of chylomicrons containing ApoB48; however, there is limited data on the intestinal synthesis and secretion of HDL-ApoA-I...
January 3, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Shanmugavel Madasamy, David Liu, Jason Lundry, Benjamin Alderete, Raymond Kong, J Paul Robinson, Alan H B Wu, Edward P Amento
Treatment of dyslipidemia patients with lipid-lowering drugs leads to a significant reduction in low-density lipoproteins (LDL) level and a low to moderate level of increase in high-density lipoprotein (HDL) cholesterol in plasma. However, a possible role of these drugs in altering morphology and distribution of cholesterol particles is poorly understood. Here, we describe the in vitro evaluation of lipid-lowering drug effects in modulating morphological features of cholesterol particles using the plaque array method in combination with imaging flow cytometry...
November 10, 2017: Journal of Visualized Experiments: JoVE
Anja Vogt
Elevated levels of lipoprotein(a) (Lp(a)) contribute to the risk of early and severe cardiovascular disease (CVD). Recently <50 mg/dl was recommended as the desirable level for clinical use and decision making. All established medical therapies to lower cholesterol levels have no impact on lowering Lp(a) except niacin which is all too often poorly tolerated and not obtainable everywhere. Lipoprotein apheresis is an extracorporeal treatment to lower levels of Lp(a) significantly by > 60%. In some countries it is recommended in very high risk patients with early or progressive CVD...
November 2017: Atherosclerosis. Supplements
Samantha Karr
Cardiovascular disease (CVD) is the leading cause of death among adults in the United States, and people with hyperlipidemia are at roughly twice the risk of developing CVD as compared to those with normal total cholesterol levels.1 Patients with familial hypercholesterolemia (FH) have an even greater risk of developing CVD at an earlier age; therefore, early detection and treatment are imperative to reduce cardiovascular events and premature death. Statins are the mainstay treatment for hyperlipidemia; however, the limitations of statins include treatment resistance, intolerance due to adverse events, and a lack of adherence which contribute to poor outcomes...
June 2017: American Journal of Managed Care
Harold Robert Superko, Xue-Qiao Zhao, Howard N Hodis, John R Guyton
Niacin (nicotinic acid) has been used for primary and secondary coronary heart disease prevention for over 40 years. Until recently clinical trials incorporating niacin as part of an intervention strategy consistently demonstrated reduction in clinical events and lesion improvement, including ≥6% absolute mortality reduction. Two large clinical event trials in 2011 (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) and 2014 (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) concluded that niacin added to statin therapy did not provide clinical event benefit over statin alone...
November 2017: Journal of Clinical Lipidology
Katerina Tosheska Trajkovska, Sonja Topuzovska
A key to effective treatment of cardiovascular disease is to understand the body's complex lipoprotein transport system. Reverse cholesterol transport (RCT) is the process of cholesterol movement from the extrahepatic tissues back to the liver. Lipoproteins containing apoA-I [highdensity lipoprotein (HDL)] are key mediators in RCT, whereas non-high-density lipoproteins (non-HDL, lipoproteins containing apoB) are involved in the lipid delivery pathway. HDL particles are heterogeneous; they differ in proportion of proteins and lipids, size, shape, and charge...
August 2017: Anatolian Journal of Cardiology
Angela Pirillo, Alberico L Catapano
Low high density lipoprotein cholesterol (HDL-C) levels represent an independent risk factor for cardiovascular disease; in addition to the reduced HDL-C levels commonly observed in patients at cardiovascular risk, the presence of dysfunctional HDL, i.e. HDL with reduced atheroprotective properties, has been reported. Despite the established inverse correlation between HDL-C levels and cardiovascular risk, several clinical trials with HDL-C-increasing drugs (such as niacin, CETP inhibitors or fibrate) failed to demonstrate that a significant rise in HDL-C levels translate into a cardiovascular benefit...
July 2017: Atherosclerosis. Supplements
Sony Tuteja, Lu Wang, Richard L Dunbar, Jinbo Chen, Stephanie DerOhannessian, Santica M Marcovina, Marshall Elam, Ellis Lader, Daniel J Rader
OBJECTIVE: Niacin has been used for seven decades to modulate plasma lipids, but its mechanism of action is still unclear. We sought to determine whether variants in the niacin receptor gene, hydroxyl-carboxylic receptor 2 (HCAR2), are associated with lipid response to treatment. PARTICIPANTS AND METHODS: Coding variants, rs7314976 (p.R311C) and rs2454727 (p.M317I), were genotyped in 2067 participants from the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial...
August 2017: Pharmacogenetics and Genomics
Julia Schreml, Ioanna Gouni-Berthold
Statin intolerance is usually defined as the inability of a patient to tolerate statin-treatment due to muscle-related complaints. While randomised trials show that these complaints occure with similar frequency in patients receiving placebo, namely in up to ~5% of the subjects, data from registries as well as clinical experience indicate a much higher frequency of up to ~30%. The lack of standard definition or of a diagnostic marker of statin intolerance confounds the problem. The diagnosis remains subjective based on the symptoms the patient reports...
June 16, 2017: Current Medicinal Chemistry
Kevin C Maki, Mary R Dicklin
PURPOSE OF REVIEW: This review summarizes the evidence supporting a relationship between lowering triglycerides (TGs) and TG-rich lipoprotein cholesterol (TGRL-C) levels and reduced atherosclerotic cardiovascular disease (ASCVD) event risk. RECENT FINDINGS: Data from observational investigations, including studies of genetic variants, provide evidence consistent with a causal relationship between elevations in TG and TGRL-C and greater risk for ASCVD. Randomized controlled trial evidence of ASCVD risk reduction with therapies that substantially lower TG and TGRL-C is limited by the fact that no large-scale trial results have been published from a study that enrolled subjects selected specifically on the basis of TG or TGRL-C elevation, although three such trials are underway or in the planning stages...
August 2017: Current Opinion in Lipidology
T Tran, N Lee
INTRODUCTION: Chronic pancreatitis by definition is a recurrent episode of acute pancreatitis and is commonly associated with alcoholism in the US. Another cause of chronic pancreatitis is hypertriglyceridemia (HTGP);, occurring in 1-5 percent of cases. The incidence of HTGP is higher in patients with diabetes and HIV, usually requiring triglyceride levels > 1000 mg/dL. CASE: A 33 year old man with uncontrolled type 1 diabetes and recurrent pancreatitis, first diagnosed 5 years prior, presented as a transfer from an outside hospital for a recurrent episode of HTGP...
March 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
Yi-Heng Li, Kwo-Chang Ueng, Jiann-Shing Jeng, Min-Ji Charng, Tsung-Hsien Lin, Kuo-Liong Chien, Chih-Yuan Wang, Ting-Hsing Chao, Ping-Yen Liu, Cheng-Huang Su, Shih-Chieh Chien, Chia-Wei Liou, Sung-Chun Tang, Chun-Chuan Lee, Tse-Ya Yu, Jaw-Wen Chen, Chau-Chung Wu, Hung-I Yeh
In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients...
April 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Sergio Montserrat-de la Paz, Dolores Rodriguez, Magdalena P Cardelo, Maria C Naranjo, Beatriz Bermudez, Rocio Abia, Francisco J G Muriana, Sergio Lopez
SCOPE: Macrophage plasticity allows adapting to different environments, having a dual activity in inflammatory-related diseases. Our hypothesis is that the type of dietary fatty acids into human postprandial triglyceride-rich lipoproteins (TRLs), alone or in combination with niacin (vitamin B3), could modulate the plasticity of monocytes-macrophages. METHODS AND RESULTS: We isolated TRLs at the postprandial peak from blood samples of healthy volunteers after the ingestion of a meal rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated fatty acids (LCPUFAs)...
August 2017: Molecular Nutrition & Food Research
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