Apolipoprotein E Gene Variants and Risk of Coronary Heart Disease: A Meta-Analysis

Xu, Min; Zhao, Jun; Zhang, Yu; Ma, Xu; Dai, Qi; Huang, Zhi; Wang, Bei; Wang, Lina

doi:10.1155/2016/3912175

Cited by 58 publications

(52 citation statements)

References 45 publications

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“…14 In previous studies, circulating concentrations of apolipoproteins (ApoA1 [protective factor] and ApoB [risk factor]) as well as apolipoprotein E gene variants have been associated with incident CVD in populations including older persons. 9,10 In our study, they did not have incremental predictive value. ApoA1 and ApoB are correlated with serum cholesterol (TC, HDL, and LDL), which did not relevantly improve predictive value either.…”

Section: Discussioncontrasting

confidence: 64%

“…This is partly explained by the diminished or even reversed associations between traditional risk factors and CVD in older persons . Moreover, potential other predictors of CVD in older people have been suggested, including an increased C‐reactive protein (CRP) as a marker for inflammation, symptoms of apathy, polypharmacy, cholesterol‐associated circulating apolipoproteins A1 and B, and gene variants of apolipoprotein E (APOE) …”

Section: Introductionmentioning

confidence: 99%

“…including an increased C-reactive protein (CRP) as a marker for inflammation, 3 symptoms of apathy, 7 polypharmacy, 8 cholesterol-associated circulating apolipoproteins A1 and B, and gene variants of apolipoprotein E (APOE). 9,10 While traditionally models predict a ten-year risk of CVD mortality, 4,11,12 older persons and their GPs favor models assessing risk of developing any major atherosclerotic event within a shorter time span. 13 Hence, GPs pragmatically and intuitively weigh additional factors including frailty, multimorbidity, quality of life, and life expectancy in their decision whether or not to start preventive treatment.…”

Section: Introductionmentioning

confidence: 99%

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A cardiovascular risk prediction model for older people: Development and validation in a primary care population

Bussel

Richard

Busschers

et al. 2019

J of Clinical Hypertension

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Cardiovascular risk prediction is mainly based on traditional risk factors that have been validated in middle‐aged populations. However, associations between these risk factors and cardiovascular disease (CVD) attenuate with increasing age. Therefore, for older people the authors developed and internally validated risk prediction models for fatal and non‐fatal CVD, (re)evaluated the predictive value of traditional and new factors, and assessed the impact of competing risks of non‐cardiovascular death. Post hoc analyses of 1811 persons aged 70‐78 year and free from CVD at baseline from the preDIVA study (Prevention of Dementia by Intensive Vascular care, 2006‐2015), a primary care‐based trial that included persons free from dementia and conditions likely to hinder successful long‐term follow‐up, were performed. In 2017‐2018, Cox‐regression analyses were performed for a model including seven traditional risk factors only, and a model to assess incremental predictive ability of the traditional and eleven new factors. Analyses were repeated accounting for competing risk of death, using Fine‐Gray models. During an average of 6.2 years of follow‐up, 277 CVD events occurred. Age, sex, smoking, and type 2 diabetes mellitus were traditional predictors for CVD, whereas total cholesterol, HDL‐cholesterol, and systolic blood pressure (SBP) were not. Of the eleven new factors, polypharmacy and apathy symptoms were predictors. Discrimination was moderate (concordance statistic 0.65). Accounting for competing risks resulted in slightly smaller predicted absolute risks. In conclusion, we found, SBP, HDL, and total cholesterol no longer predict CVD in older adults, whereas polypharmacy and apathy symptoms are two new relevant predictors. Building on the selected risk factors in this study may improve CVD prediction in older adults and facilitate targeting preventive interventions to those at high risk.

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Section: Discussioncontrasting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A cardiovascular risk prediction model for older people: Development and validation in a primary care population

Bussel

Richard

Busschers

et al. 2019

J of Clinical Hypertension

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“…Levels of plasma APOE and, generally also, high-density lipoprotein cholesterol (HDL-C) decrease in a perfect parametric fashion across the six APOE genotypes (2/2 > 2/3 > 2/4 > 3/3 > 3/4 > 4/4; Figure 4A), and the reverse is true for levels of low-density lipoprotein cholesterol (LDL-C; Figure 4B) (Bennet et al, 2007;Khan et al, 2013;Rasmussen, 2016). A similar stepwise pattern is seen in the risk for coronary artery disease (CAD) and myocardial infarction (MI), where APOE2 carriers have the least risk, APOE4 carriers have the greatest risk, and APOE3 carriers fall in the middle (Anand et al, 2009;Bennet et al, 2007;Wang et al, 2015;Xu et al, 2016; Figure 4E). For comparison, the risk for AD across genotypes is shown in Figure 4D.…”

Section: Cardiovascular Diseasementioning

confidence: 80%

A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward

Belloy

Napolioni

Greicius

2019

Neuron

403

354

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Alzheimer's disease (AD) is considered a polygenic disorder. This view is clouded, however, by lingering uncertainty over how to treat the quasi ''monogenic'' role of apolipoprotein E (APOE). The APOE4 allele is not only the strongest genetic risk factor for AD, it also affects risk for cardiovascular disease, stroke, and other neurodegenerative disorders. This review, based mostly on data from human studies, ranges across a variety of APOE-related pathologies, touching on evolutionary genetics and risk mitigation by ethnicity and sex. The authors also address one of the most fundamental question pertaining to APOE4 and AD: does APOE4 increase AD risk via a loss or gain of function? The answer will be of the utmost importance in guiding future research in AD. (A) The three main APOE isoforms APOE2, APOE3, and APOE4, respectively, encoded by the Apolipoprotein E2, E3, and E4 alleles, are the result of non-synonymous polymorphisms that cause amino acid changes at position 112 and 158 of the APOE protein (Rall et al., 1982; Weisgraber et al., 1981). APOE3 is the most common variant in the general population. The APOE4 variant is a major genetic risk factor for AD, while APOE2 is protective (Farrer et al., 1997). (B) Structural models of lipid-free APOE are shown for each major isoform, based on X-ray crystallography, structure prediction, and circular dichroism spectroscopy (Zhong and Weisgraber, 2009). The N-terminal domain contains APOE's low-density lipoprotein receptor (LDLR) region at amino acid residues 134-150, while the C-terminal holds the lipid-binding region at residues 244-272. Amino acid substitutions in APOE4 promote a salt bridge between Arg61 and Glu255, which, compared to the APOE2 and APOE3 variants, drives increased domain interaction between the N-and C-terminal domains. In (A), APOE allele frequencies are obtained, with permission, from American

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“…These include lipoproteins metabolisms, cholesterols transport, tissue repair, immune response and regulation, as well as cell growth and differentiation. The localization,frequencies and biological pathways in both CVD and cancer patients have been studied elsewhere in terms of CVD, neurological dysfunction, neuromuscular diseases and different types of diabetes67, 68 .…”

mentioning

confidence: 99%

Meta-regression analysis of the effect of lifestyle interventions on mediators of inflammation in postmenopausal breast cancer women with cardiovascular risk factors

Milambo

Kotze

Rajiv

et al. 2019

Preprint

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Background: Chronic inflammation is associated with obesity, dyslipidemia, and different types of malignancies that may play a complex role in the risk of breast cancer (BC) recurrence and therapy related side effects. The purpose of this review was to determine the effects of lifestyle interventions on mediators of inflammation (C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α)) and other therapy related adverse events in postmenopausal BCS with cardiovascular related risk factors. Methods: A systematic search for relevant articles was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis criteria using available databases (PubMed, Scopus, The Cochrane Library, OpenGrey, Google Scholar and CENTRAL). Results: Twelve eligible randomized controlled trials (RCT) met the inclusion criteria. The mean ages of postmenopausal BC women ranged from 49 to 56 years. The meta-regression revealed that there was moderate evidence that MSE decreased the mean difference (MD) of inflammatory markers in BCS, with CVD risk factors (MD: 0.31; 95% CI: 0.05 to 0.57, P=0.02; heterogeneity: Tau² = 0. 12; Chi² = 106.30, df = 19, I² = 0. 50.4%). Conclusion: There is a moderate level of evidence on the effects of MSE on mediators of inflammation in postmenopausal BCS with cardiovascular risk factors. A number of shared risk factors between postmenopausal status and CVD should be considered, while treating postmenopausal BCS.

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Apolipoprotein E Gene Variants and Risk of Coronary Heart Disease: A Meta-Analysis

Cited by 58 publications

References 45 publications

A cardiovascular risk prediction model for older people: Development and validation in a primary care population

A cardiovascular risk prediction model for older people: Development and validation in a primary care population

A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward

Meta-regression analysis of the effect of lifestyle interventions on mediators of inflammation in postmenopausal breast cancer women with cardiovascular risk factors

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