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      Establishing a threshold to predict risk of cardiovascular disease from the serum triglyceride and high-density lipoprotein concentrations in persons with spinal cord injury

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          Abstract

          Study Design

          Retrospective Cohort

          Objective

          This report identified the serum triglyceride (TG) concentrations in persons with spinal cord injury (SCI) and able-bodied (AB) individuals that the serum high-density lipoprotein cholesterol (HDL-C) equaled 40 mg/dl, a concentration below which is an independent risk factor for coronary artery disease.

          Methods

          Retrospective analysis was performed on 578 participants: 223 with SCI at or proximal to the 4 th thoracic vertebrae (↑T4), 178 with SCI at or distal to the 5 th thoracic vertebrae (↓T5), and 177 AB. Different statistical modeling approaches identified the intersecting serum TG concentration with a serum HDL-C concentration equal to 40 mg/dl. Participants were dichotomized into subgroups by TG concentration exceeding (Supra) or falling below (Sub) the intersecting value and the TG/HDL-C ratios were compared.

          Results

          Linear regression analysis revealed that the serum TG concentration that intersects with serum HDL-C concentration at 40 mg/dl was 121 mg/dl in SCI ↑T4 and 137 mg/dl in SCI ↓T5 group. A receiver operating characteristic curve identified the optimal TG concentration as 115 mg/dl in SCI ↑T4 and 137 mg/dl in SCI ↓T5 group with the latter concentration being similar to the AB group (e.g., 137 mg/dl). The TG/HDL-C ratios in the respective ↑T4, ↓T5, and AB Supra and Sub groups were similar within each group.

          Conclusions

          A lower TG concentration appears to be associated with dyslipidemia in persons with SCI than AB individuals. These findings should prompt clinicians to screen for and consider instituting lifestyle or pharmacological interventions at lower TG concentrations to reduce risk of CVD.

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          Most cited references37

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          Mechanism of action of fibrates on lipid and lipoprotein metabolism.

          Treatment with fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations. Recent investigations indicate that the effects of fibrates are mediated, at least in part, through alterations in transcription of genes encoding for proteins that control lipoprotein metabolism. Fibrates activate specific transcription factors belonging to the nuclear hormone receptor superfamily, termed peroxisome proliferator-activated receptors (PPARs). The PPAR-alpha form mediates fibrate action on HDL cholesterol levels via transcriptional induction of synthesis of the major HDL apolipoproteins, apoA-I and apoA-II. Fibrates lower hepatic apoC-III production and increase lipoprotein lipase--mediated lipolysis via PPAR. Fibrates stimulate cellular fatty acid uptake, conversion to acyl-CoA derivatives, and catabolism by the beta-oxidation pathways, which, combined with a reduction in fatty acid and triglyceride synthesis, results in a decrease in VLDL production. In summary, both enhanced catabolism of triglyceride-rich particles and reduced secretion of VLDL underlie the hypotriglyceridemic effect of fibrates, whereas their effect on HDL metabolism is associated with changes in HDL apolipoprotein expression.
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            Diabetic dyslipidemia.

            Diabetic dyslipidemia is characterized by elevated fasting and postprandial triglycerides, low HDL-cholesterol, elevated LDL-cholesterol and the predominance of small dense LDL particles. These lipid changes represent the major link between diabetes and the increased cardiovascular risk of diabetic patients. The underlying pathophysiology is only partially understood. Alterations of insulin sensitive pathways, increased concentrations of free fatty acids and low grade inflammation all play a role and result in an overproduction and decreased catabolism of triglyceride rich lipoproteins of intestinal and hepatic origin. The observed changes in HDL and LDL are mostly sequence to this. Lifestyle modification and glucose control may improve the lipid profile but statin therapy mediates the biggest benefit with respect to cardiovascular risk reduction. Therefore most diabetic patients should receive statin therapy. The role of other lipid lowering drugs, such as ezetimibe, fibrates, omega-3 fatty acids, niacin and bile acid sequestrants is less well defined as they are characterized by largely negative outcome trials. This review examines the pathophysiology of diabetic dyslipidemia and its relationship to cardiovascular diseases. Management approaches will also be discussed.
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              LDL Particle Number and Risk of Future Cardiovascular Disease in the Framingham Offspring Study - Implications for LDL Management.

              The cholesterol content of LDL particles is variable, causing frequent discrepancies between concentrations of LDL cholesterol and LDL particle number. In managing patients at risk for cardiovascular disease (CVD) to LDL target levels, it is unclear whether LDL cholesterol provides the optimum measure of residual risk and adequacy of LDL lowering treatment. To compare the ability of alternative measures of LDL to provide CVD risk discrimination at relatively low levels consistent with current therapeutic targets. Concentrations of LDL cholesterol (LDL-C) and non-HDL cholesterol (non-HDL-C) were measured chemically and LDL particle number (LDL-P) and VLDL particle number (VLDL-P) were measured by nuclear magnetic resonance (NMR) in 3066 middle-aged white participants (53% women) without CVD in the Framingham Offspring cohort. The main outcome measure was incidence of first CVD event. At baseline, the cholesterol content per LDL particle was negatively associated with triglycerides and positively associated with LDL-C. On follow-up (median 14.8 yrs), 265 men and 266 women experienced a CVD event. In multivariable models adjusting for non-lipid CVD risk factors, LDL-P was related more strongly to future CVD in both sexes than LDL-C or non-HDL-C. Subjects with a low level of LDL-P (<25(th) percentile) had a lower CVD event rate (59 events per 1000 person-years) than those with an equivalently low level of LDL-C or non-HDL-C (81 and 74 events per 1000 person-years, respectively). In a large community-based sample, LDL-P was a more sensitive indicator of low CVD risk than either LDL-C or non-HDL-C, suggesting a potential clinical role for LDL-P as a goal of LDL management.
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                Author and article information

                Journal
                9609749
                20400
                Spinal Cord
                Spinal Cord
                Spinal cord
                1362-4393
                1476-5624
                25 July 2018
                08 August 2018
                November 2018
                01 May 2019
                : 56
                : 11
                : 1051-1058
                Affiliations
                [1 ]Department of Veterans Affairs Rehabilitation Research & Development Service National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA
                [2 ]Department of Physical Therapy, School of Health and Medical Sciences, Seton Hall University, South Orange, NJ, USA
                [3 ]The Institute for Advanced Study of Rehabilitation and Sports Science, School of Health and Medical Sciences, Seton Hall University, South Orange, NJ, USA
                [4 ]Departments of Medical Sciences and Neurology, Hackensack Meridian School of Medicine at Seton Hall University, Nutley, NJ, USA
                [5 ]Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA
                [6 ]Kessler Foundation, West Orange, NJ, USA
                [7 ]Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, NJ, USA
                [8 ]Kessler Institute for Rehabilitation, West Orange, NJ, USA
                [9 ]Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
                [10 ]Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
                Author notes
                Address for Correspondence and Reprints: Michael F. La Fountaine, EdD, ATC, FACSM, National Center for the Medical Consequences of Spinal Cord Injury, michael.lafountaine@ 123456va.gov
                Article
                VAPA1500765
                10.1038/s41393-018-0187-7
                6219899
                30089895
                d22d008c-397b-4a15-9495-8565929751c2

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                History
                Categories
                Article

                Neurology
                liver,lipids and lipoproteins,tg/hdl-c ratio,paraplegia,quadriplegia,spinal cord injuries
                Neurology
                liver, lipids and lipoproteins, tg/hdl-c ratio, paraplegia, quadriplegia, spinal cord injuries

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