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      Small Dense Low-Density Lipoproteins and Associated Risk Factors in Patients with Stroke

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          Abstract

          Objective: Low-density lipoproteins (LDL) are a heterogeneous group of particles, with small, dense particles being more atherogenic. It remains controversial whether elevated plasma levels of small dense LDL (sd-LDL) are risk factors for stroke. The aim of the present study was to examine the plasma levels of sd-LDL in patients with stroke and to investigate the associations in a large Chinese case-control study. Methods: We recruited 299 stroke patients (159 cerebral thrombosis, 42 lacunar infarction, 98 intracerebral hemorrhage) and 299 controls. The semiquantitative analysis of plasma levels of sd-LDL was performed by nondenaturing gradient gel electrophoresis. Results: (1) The plasma levels of sd-LDL in patients with ischemic stroke or hemorrhagic stroke were higher than in controls. (2) Multiple regression analysis showed that there were significant relationships between sd-LDL and triglyceride, high-density lipoprotein cholesterol, LDL cholesterol, systolic blood pressure and history of diabetes, and a significant relationship between sd-LDL and stroke (r = 0.286, p < 0.001) even after adjusting for these factors. (3) Compared with the controls, the calculation of odds ratios indicated relative risk estimates of 3.111 for ischemic stroke (OR = 3.111 , 95% CI = 1.891–5.117, p < 0.001) and 3.164 for hemorrhagic stroke (OR = 3.164, 95% CI = 1.632–6.137, p < 0.01). Conclusion: Plasma sd-LDL was independently associated with both thrombotic and hemorrhagic stroke, suggesting it may be an independent predictor of as well as a risk factor for stroke in Chinese people, justifying clinical trials for primary and secondary prevention of stroke using statins or fibrates.

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          A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction.

          M Stampfer, R Krauss, J. Ma … (1996)
          To test whether a predominance of small, dense low-density lipoprotein (LDL) particles and elevated triglyceride levels are independent risk factors for myocardial infarction (MI). Nested case-control study with prospectively collected samples. Prospective cohort study. Blood samples were collected at baseline (85% nonfasting samples) from 14916 men aged 40 to 84 years in the Physicians' Health Study. Myocardial infarction diagnosed during 7 years of follow-up. Cases (n=266) had a significantly smaller LDL diameter (mean [SD], 25.6 [0.9] nm) than did controls (n=308) matched on age and smoking (mean [SD], 25.9 [8] nm; P<.001). Cases also had higher median triglyceride levels (1.90 vs 1.49 mmol/L [168 vs 132 mg/dL]; P<.001). The LDL diameter had a high inverse correlation with triglyceride level (r=-0.71), and a high direct correlation with high-density lipoprotein cholesterol (HDL-C) level (r=0.60). We observed a significant multiplicative interaction between triglyceride and total cholesterol (TC) levels (P=.01). After simultaneous adjustment for lipids and a variety of coronary risk factors, LDL particle diameter was no longer a statistically significant risk indicator, with a relative risk (RR) of 1.09 (95% confidence interval [CI], 0.85-1.40) per 0.8-nm decrease. However, triglyceride level remained significant with an RR of 1.40 (95% CI, 1.10-1.77) per 1.13 mmol/L (100-mg/dL) increase. The association between triglyceride level and MI risk appeared linear across the distribution; men in the highest quintile had a risk about 2.5 times that of those in the lowest quintile. The TC level, but not HDL-C level, also remained significant, with an RR of 1.80 (95% CI, 1.44-2.26) per 1.03-mmol/L (40-mg/dL) increase. These findings indicate that nonfasting triglyceride levels appear to be a strong and independent predictor of future risk of MI, particularly when the total cholesterol level is also elevated. In contrast, LDL particle diameter is associated with risk of MI, but not after adjustment for triglyceride level. Increased triglyceride level, small LDL particle diameter, and decreased HDL-C levels appear to reflect underlying metabolic perturbations with adverse consequences for risk of MI; elevated triglyceride levels may help identify high-risk individuals.
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            Low-density lipoprotein subclass patterns and risk of myocardial infarction.

            B Krauss, Jonathan W. Willett, Charles Hennekens … (1988)
            The association of low-density lipoprotein (LDL) subclass patterns with coronary heart disease was investigated in a case-control study of nonfatal myocardial infarction. Subclasses of LDL were analyzed by gradient gel electrophoresis of plasma samples from 109 cases and 121 controls. The LDL subclass pattern characterized by a preponderance of small, dense LDL particles was significantly associated with a threefold increased risk of myocardial infarction, independent of age, sex, and relative weight. Plasma levels of high-density lipoprotein cholesterol were decreased, and levels of triglyceride, very low-density lipoproteins, and intermediate-density lipoproteins were increased in subjects with this LDL subclass pattern. Multivariate logistic regression analyses showed that both high-density lipoprotein cholesterol and triglyceride levels contributed to the risk associated with the small, dense LDL subclass pattern. Thus, the metabolic trait responsible for this LDL subclass pattern results in a set of interrelated lipoprotein changes that lead to increased risk of coronary heart disease.
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              Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk.

              Alasdair Freeman, M Caslake, Stephen Tait … (1994)
              The concentration of plasma LDL subfractions is described in four groups of normocholesterolaemic (total plasma cholesterol < 6.5 mmol/l) male subjects consisting of men with and without coronary artery disease (CAD+/-), as determined by angiography, post-myocardial infarct survivors (PMI) and normal, healthy controls. The CAD(+) and PMI groups were distinguished from the CAD(-) and controls by raised concentrations of plasma triglyceride, very low density lipoprotein (VLDL) cholesterol, small, dense LDL (LDL-III density (d) 1.044-1.060 g/ml) and lower concentrations of high density lipoprotein (HDL) cholesterol and large, buoyant LDL (LDL-I d 1.025-1.034 g/ml). In all groups, a subfraction of intermediate density, LDL-II (d 1.034-1.044 g/ml), was the predominant LDL species but was not related to coronary heart disease risk. Plasma triglyceride showed a positive association with LDL-II (r = 0.51, P < 0.001) below a triglyceride level of 1.5 mmol/l. Above this threshold of 1.5 mmol/l, LDL-II and LDL-I showed significant negative associations with triglyceride (LDL-II r = -0.5, P < 0.001; LDL-I r = -0.45, P < 0.001). Small, dense LDL-III showed a weak positive association with triglyceride that became highly significant above the 1.5 mmol/l threshold (r = 0.54, P < 0.001). While age was positively related to LDL-II within the control subjects (r = 0.3, P < 0.05), there was no difference in the percentage abundance or concentration of LDL-III within control and CAD(-) subjects above and below the age of 40 years. Smoking was associated with a relative deficiency of the LDL-I subfraction (LDL-I to LDL-III ratio in smokers = 0.77, in ex-smokers = 0.95, in non-smokers = 1.89; P < 0.01), as was beta-blocker medication (% LDL-I, users vs. non-users, P < 0.05). Both of these effects could be explained by their primary influence on plasma triglyceride. Analysis of the frequency distributions for the three LDL subfractions revealed the concentration of small, dense LDL-III to be bimodal around a concentration of 100 mg (lipoprotein mass)/100 ml plasma. The calculation of odds ratios based on this figure indicated relative risk estimates of 4.5 (chi 2: P < 0.01) for the presence of coronary artery disease and 6.9 (chi 2: P < 0.001) for myocardial infarction.(ABSTRACT TRUNCATED AT 400 WORDS)
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                Author and article information

                Journal
                Journal ID (publisher-id): CED
                Journal ID (nlm-ta): Cerebrovasc Dis
                Journal ID (doi): 10.1159/issn.1015-9770
                Title: Cerebrovascular Diseases
                Publisher: S. Karger AG
                ISSN (Print): 1015-9770
                ISSN (Electronic): 1421-9786
                Publication date Subscription-year: 2009
                Publication date (Print): January 2009
                Publication date (Electronic): 22 November 2008
                Volume: 27
                Issue: 1
                Pages: 99-104
                Affiliations
                aInstitute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, and bFuwai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, PR China; cCentre de Recherche Laval Hospital, Laval University, Quebec City, Que., Canada
                Article
                Publisher ID: 175768 Other ID: Cerebrovasc Dis 2009;27:99–104
                DOI: 10.1159/000175768
                PubMed ID: 19033685
                SO-VID: 2ca034be-ae5a-4ca9-a889-f2f148e15a31
                Copyright © © 2008 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 04 February 2008
                Date accepted : 19 August 2008
                Page count
                Tables: 3, References: 32, Pages: 6
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Geriatric medicine,Neurology,Cardiovascular Medicine,Neurosciences,Clinical Psychology & Psychiatry,Public health
                Keywords: Risk factors,Stroke,Chinese people, small dense low-density lipoproteins
                Data availability:
                ScienceOpen disciplines: Geriatric medicine, Neurology, Cardiovascular Medicine, Neurosciences, Clinical Psychology & Psychiatry, Public health
                Keywords: Risk factors, Stroke, Chinese people, small dense low-density lipoproteins

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