Dataset Information

Low-Density Lipoprotein Cholesterol and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

ABSTRACT: Objective: To assess the association between low-density lipoprotein cholesterol (LDL-c) and risk of Alzheimer's disease (AD). Methods: Embase, Pubmed, and Web of Science were searched until June 2019. Standard mean difference (SMD) with 95% confidence intervals (CI) was estimated using random-effects models. Results: Our meta-analysis of 26 studies revealed higher levels of LDL-c in AD than that of non-dementia controls (SMD = 0.35, 95% CI 0.12-0.58, p < 0.01). The meta-regression analysis on confounders showed that age (p < 0.01, Adj R-squared = 92.41%) and cardiovascular disease (p = 0.01, Adj R-squared = 85.21%), but not the body mass index, education, smoking, hypertension and diabetes mellitus, exerted an impact on the relationship between LDL-c and risk of ICH. Further subgroup analysis of age showed LDL-c levels in AD patients aged 60-70 were higher than that of non-dementia (60 ? age < 70: SMD = 0.80, 95% CI 0.23-1.37, p < 0.01); but no association between the SMD of AD in LDL-c and age over 70 was noted across the studies (70 ? age < 77: SMD = -0.02, 95% CI -0.39~0.34, p = 9.0; 77 ? age < 80: SMD = 0.15, 95% CI -0.17~0.47, p = 0.35; ?80: SMD = 0.53, 95% CI -0.04~1.11, p = 0.07). The concentrations of LDL-c during the quintile interval of 3~4 were positively associated with AD (121 ? concentration < 137: SMD = 0.98, 95% CI 0.13~1.82, p = 0.02; ?137: SMD = 0.62, 95% CI 0.18~1.06, p < 0.01); whereas there was no correlation between AD and LDL-c within the quintile interval of 1~2 (103.9 ? concentration < 112: SMD = 0.08, 95% CI -0.20~0.35, p = 0.59; 112 ? concentration < 121: SMD = -0.26, 95% CI -0.58~0.06, p = 0.11). Conclusions: Elevated concentration of LDL-c (>121 mg/dl) may be a potential risk factor for AD. This association is strong in patients aged 60-70 years, but vanishes with advancing age.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC7002548 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Low-Density Lipoprotein Cholesterol and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Zhou Zhike Z Liang Yifan Y Zhang Xiaoqian X Xu Junjie J Lin Jueying J Zhang Rongwei R Kang Kexin K Liu Chang C Zhao Chuansheng C Zhao Mei M

Frontiers in aging neuroscience 20200130

Objective: To assess the association between low-density lipoprotein cholesterol (LDL-c) and risk of Alzheimer's disease (AD). Methods: Embase, Pubmed, and Web of Science were searched until June 2019. Standard mean difference (SMD) with 95% confidence intervals (CI) was estimated using random-effects models. Results: Our meta-analysis of 26 studies revealed higher levels of LDL-c in AD than that of non-dementia controls (SMD = 0.35, 95% CI 0.12-0.58, p < 0.01). The m ...[more]

PMID: 32082137

Similar Datasets

Project description:OBJECTIVES:To determine by how much statins reduce serum concentrations of low density lipoprotein (LDL) cholesterol and incidence of ischaemic heart disease (IHD) events and stroke, according to drug, dose, and duration of treatment. DESIGN:Three meta-analyses: 164 short term randomised placebo controlled trials of six statins and LDL cholesterol reduction; 58 randomised trials of cholesterol lowering by any means and IHD events; and nine cohort studies and the same 58 trials on stoke. MAIN OUTCOME MEASURES:Reductions in LDL cholesterol according to statin and dose; reduction in IHD events and stroke for a specified reduction in LDL cholesterol. RESULTS:Reductions in LDL cholesterol (in the 164 trials) were 2.8 mmol/l (60%) with rosuvastatin 80 mg/day, 2.6 mmol/l (55%) with atorvastatin 80 mg/day, 1.8 mmol/l (40%) with atorvastatin 10 mg/day, lovastatin 40 mg/day, simvastatin 40 mg/day, or rosuvastatin 5 mg/day, all from pretreatment concentrations of 4.8 mmol/l. Pravastatin and fluvastatin achieved smaller reductions. In the 58 trials, for an LDL cholesterol reduction of 1.0 mmol/l the risk of IHD events was reduced by 11% in the first year of treatment, 24% in the second year, 33% in years three to five, and by 36% thereafter (P < 0.001 for trend). IHD events were reduced by 20%, 31%, and 51% in trials grouped by LDL cholesterol reduction (means 0.5 mmol/l, 1.0 mmol/l, and 1.6 mmol/l) after results from first two years of treatment were excluded (P < 0.001 for trend). After several years a reduction of 1.8 mmol/l would reduce IHD events by an estimated 61%. Results from the same 58 trials, corroborated by results from the nine cohort studies, show that lowering LDL cholesterol decreases all stroke by 10% for a 1 mmol/l reduction and 17% for a 1.8 mmol/l reduction. Estimates allow for the fact that trials tended to recruit people with vascular disease, among whom the effect of LDL cholesterol reduction on stroke is greater because of their higher risk of thromboembolic stroke (rather than haemorrhagic stroke) compared with people in the general population. CONCLUSIONS:Statins can lower LDL cholesterol concentration by an average of 1.8 mmol/l which reduces the risk of IHD events by about 60% and stroke by 17%.

Project description:BACKGROUND: Low plasma high-density lipoprotein cholesterol (HDL-C) levels are a strong, independent, but poorly understood risk factor for cardiovascular disease (CVD). Although this atherogenic lipid abnormality has been widely reported in Australia's Indigenous peoples, Aboriginal and Torres Strait Islanders, the evidence has not come under systematic review. This review therefore examines published data for Indigenous Australians reporting 1) mean HDL-C levels for both sexes and 2) factors associated with low HDL-C. METHODS: PubMed, Medline and Informit ATSI Health databases were systematically searched between 1950 and 2012 for studies on Indigenous Australians reporting mean HDL-C levels in both sexes. Retrieved studies were evaluated by standard criteria. Low HDL-C was defined as: <1.0 mmol/L. Analyses of primary data associating measures of HDL-C with other CVD risk factors were also performed. RESULTS: Fifteen of 93 retrieved studies were identified for inclusion. These provided 58 mean HDL-C levels; 29 for each sex, most obtained in rural/regional (20%) or remote settings (60%) and including 51-1641 participants. For Australian Aborigines, mean HDL-C values ranged between 0.81-1.50 mmol/L in females and 0.76-1.60 mmol/L in males. Two of 15 studies reported HDL-C levels for Torres Strait Islander populations, mean HDL-C: 1.00 or 1.11 mmol/L for females and 1.01 or 1.13 mmol/L for males. Low HDL-C was observed only in rural/regional and remote settings--not in national or urban studies (n?=?3) in either gender. Diabetes prevalence, mean/median waist-to-hip ratio and circulating C-reactive protein levels were negatively associated with HDL-C levels (all P?<?0.05). Thirty-four per cent of studies reported lower mean HDL-C levels in females than in males. CONCLUSIONS: Very low mean HDL-C levels are common in Australian Indigenous populations living in rural and remote communities. Inverse associations between HDL-C and central obesity, diabetes prevalence and inflammatory markers suggest a particularly adverse CVD risk factor profile. An absence of sex dichotomy in HDL-C levels warrants further investigation.

Project description:Background Epidemiological studies show that women are generally at lower risk for cardiovascular disease than men. Here, we investigated the sex-specific differential effect of genetically increased low-density lipoprotein cholesterol (LDL-C) on cardiovascular disease (CVD) and other lipid-associated diseases. Methods and Results This is a 2-sample Mendelian randomization study that uses individual participant data from 425 043 participants from the UK Biobank, including 229 279 female participants. An 80-variant LDL-C weighted genetic score was generated. Linear and logistic regression models with interactions were used to identify differences between sex-specific LDL-C effects on lipids, carotid-intima media thickness, and multiple cardiovascular outcomes such as CVD, ischemic heart disease, peripheral artery disease, heart failure, aortic valve disease, type 2 diabetes, atrial fibrillation, and aortic aneurysm and dissection. After correction for multiple testing, we observed that the genetically increased LDL-C effect on CVD events was sex specific: per SD genetically increased LDL-C, female participants had a higher LDL-C increase but an attenuated CVD risk increase compared with male participants (LDL-C: female participants 0.71 mmol/L, 95% CI, 0.70-0.72 and male participants 0.57 mmol/L, 95% CI, 0.56-0.59. P for interaction: 5.03×10-60; CVD: female participants: odds ratio [OR], 1.32; 95% CI 1.24-1.40 and male participants: OR, 1.52; 95% CI, 1.46-1.58. P for interaction: 9.88×10-5). We also observed attenuated risks for ischemic heart disease and (nominally for) heart failure in female participants, and genetically increased LDL-C results in higher risk for aortic valve disease in female participants compared with male participants. Genetically increased LDL-C was also associated with an attenuated carotid-intima media thickness increase in female participants. We did not observe other significant attenuations. Sensitivity analyses with an unweighted genetic score and sex-specific weighted genetic scores showed similar results. Conclusions We found that genetically increased LDL-C has a sex-specific differential effect on the risk for cardiovascular disease, ischemic heart disease, heart failure, and aortic valve stenosis. Our observations provide evidence that LDL-C might be a less important determinant of CVD in women compared with men, suggesting that male patients might benefit more from LDL-C targeted therapies for CVD management than female patients and warranting investigations into the sex-specific relative contribution of risk factors for CVD.

Project description:Levels of LDL (low-density lipoprotein) cholesterol in the population are declining, and increasing attention is being focused on residual lipid-related pathways of atherosclerotic cardiovascular disease risk beyond LDL cholesterol. Among individuals with low (<130 mg/dL) LDL cholesterol, we undertook detailed profiling of circulating atherogenic lipoproteins in relation to incident cardiovascular disease in 2 populations. We performed proton nuclear magnetic resonance spectroscopy to quantify concentrations of LDL and VLDL (very low-density lipoprotein) particle subclasses in 11 984 JUPITER trial participants (NCT00239681). Adjusted Cox models examined cardiovascular disease risk associated with lipoprotein measures according to treatment allocation. Risk (adjusted hazard ratio [95%CI] per SD increment) among placebo-allocated participants was associated with total LDL particles (1.19 [1.02, 1.38]) and total VLDL particles (1.21 [1.04, 1.41]), as well as apolipoprotein B, non-high-density lipoprotein cholesterol, and triglycerides, but not LDL-c. Rosuvastatin reduced LDL measures but had variable effects on triglyceride and VLDL measures. On-statin levels of the smallest VLDL particle subclass were associated with a 68% per-SD (adjusted hazard ratio 1.68 [1.28, 2.22]) increase in residual risk-this risk was related to VLDL cholesterol and not triglyceride or larger VLDL particles. There was evidence that residual risk prediction during statin therapy could be significantly improved through the inclusion of key VLDL measures (Harrell C-index 0.780 versus 0.712; P<0.0001). In an independent, prospective cohort of 4721 individuals referred for cardiac catheterization (CATHGEN), similar patterns of lipoprotein-related risk were observed. Atherogenic lipoprotein particle concentrations were associated with cardiovascular disease risk when LDL cholesterol was low. VLDL lipoproteins, particularly the smallest remnant subclass, may represent unused targets for risk prediction and potential therapeutic intervention for reducing residual risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Dataset Information

Low-Density Lipoprotein Cholesterol and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Publications

Low-Density Lipoprotein Cholesterol and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets