Elevated Blood Homocysteine and Risk of Alzheimer’s Dementia: An Updated Systematic Review and Meta-Analysis Based on Prospective Studies

Author(s):  
M. Zuin ◽  
C. Cervellati ◽  
G. Brombo ◽  
A. Trentini ◽  
L. Roncon ◽  
...  

Objective: To investigate whether high serum homocysteine (Hcy) levels is associated with the risk of developing Alzheimer’s disease (AD) by performing a meta-analysis based on updated published data. Methods: We conducted a comprehensive research using Medline (Pubmed), Scopus, Web of Science and EMBASE databases to identify all prospective studies published any time to July 7, 2020 evaluating the association between elevated Hcy levels and AD risk. Results: From an initial screening of 269 published papers, 9 prospective investigations conducted on a total of 7474 subjects with mean follow-up of 9.5 years (range: 3.7-10) were included in the meta-analysis. Eight seventy-five of these subjects converted to AD. Hcy was significantly higher in these individuals (HRadjusted:1.48, 95% CI:1.23-1.76, I2=65.6%, p<0.0001) compared with who did not convert to AD. There was a significant publication bias (Egger’s test, t=6.39, p=0.0003) and this was overcome by the trim and fill method, which allowed to calculate a bias-corrected imputed risk estimate of HRadjusted:1.20, 95% CI:1.01-1.44, Q value=41.92. Conclusions: The present meta-analysis found that having higher Hcy increases the risk of AD in the elderly and this finding is consistent with the widely suggested role of this non-proteinogenic α-amino acid in AD neurodegeneration.

2019 ◽  
Vol 104 (10) ◽  
pp. 4539-4551 ◽  
Author(s):  
Li Jiang ◽  
Kai Wang ◽  
Kenneth Lo ◽  
Yueyang Zhong ◽  
Aimin Yang ◽  
...  

AbstractContextAlthough the role of iron in the development of type 2 diabetes (T2D) has long been a concern, prospective studies directly linking body iron stores to T2D risk in a sex-dependent context have been inconsistent.ObjectiveA systematic meta-analysis was conducted to explore the sex-specific association of circulating ferritin with T2D risk.Data SourcesWe searched PubMed, Web of Science, and EMBASE databases to identify available prospective studies through 1 August 2018.ResultsFifteen prospective studies comprising 77,352 participants and 18,404 patients with T2D, aged 20 to 80 years, and with ∼3 to 17 years of follow-up were identified. For each 100-μg/L increment in ferritin levels of overall participants, T2D risk increased by 22% (RR, 1.22; 95% CI, 1.14 to 1.31). Of note, major heterogeneities by sex were identified, with increased ferritin level having an apparently greater effect on T2D risk in women (RR, 1.53; 95% CI, 1.29 to 1.82) than in men (RR, 1.21; 95% CI, 1.15 to 1.27) after exclusion of a study with high heterogeneity (41,512 men and 6974 women for sex-specific analyses; P = 0.020 for sex difference). Further nonlinear analysis between circulating ferritin and T2D risk also showed sex-dimorphic association in that the T2D risk of women was twice as strong in magnitude as that of men at the same ferritin level.ConclusionsGreater circulating ferritin levels were independently associated with increased T2D risk, which appeared stronger among women than men. Our findings provide prospective evidence for further testing of the utility of ferritin levels in predicting T2D risk in a sex-specific manner.


2014 ◽  
Vol 18 (4) ◽  
pp. 695-704 ◽  
Author(s):  
Rosana Poggio ◽  
Laura Gutierrez ◽  
María G Matta ◽  
Natalia Elorriaga ◽  
Vilma Irazola ◽  
...  

AbstractObjectiveThe purpose of the present study was to determine whether elevated dietary Na intake could be associated with CVD mortality.DesignWe performed a systematic review and meta-analysis of prospective studies representing the general population. The adjusted relative risks and their 95 % confidence intervals were pooled by the inverse variance method using random-effects models. Heterogeneity, publication bias, subgroup and meta-regression analyses were performed.SettingsMEDLINE (since 1973), Embase (since 1975), the Cochrane Library (since 1976), ISI Web of Science, Google Scholar (until September 2013) and secondary referencing were searched for inclusion in the study.SubjectEleven prospective studies with 229 785 participants and average follow-up period of 13·37 years (range 5·5–19 years).ResultsHigher Na intake was significantly associated with higher CVD mortality (relative risk=1·12; 95 % CI 1·06, 1·19). In the sensitivity analysis, the exclusion of studies with important relative weights did not significantly affect the results (relative risk=1·08; 95 % CI 1·01, 1·15). The meta-regression analysis showed that for every increase of 10 mmol/d in Na intake, CVD mortality increased significantly by 1 % (P=0·016). Age, hypertensive status and length of follow-up were also associated with increased CVD mortality.ConclusionsHigher Na intake was associated with higher CVD mortality in the general population; this result suggests a reduction in Na intake to prevent CVD mortality from any cause.


2001 ◽  
Vol 85 (04) ◽  
pp. 626-633 ◽  
Author(s):  
Augusto Di Castelnuovo ◽  
Giovanni de Gaetano ◽  
Maria Benedetta Donati ◽  
Licia Iacoviello

SummaryMembrane glycoprotein IIb/IIIa plays a major role in platelet function. The gene encoding the glycoprotein IIIa shows a common polymorphism PlA1/PlA2 that was variably associated with vascular disease. To clarify the role of PlA1/PlA2 polymorphism in coronary risk, a meta-analysis of published data was conducted. Studies were identified both by MEDLINE searches, and hand searching of journals and abstract books.A total of 34 studies for coronary artery disease (CAD), and 6 for restenosis after revascularization were identified, for a total of 9,095 cases and 12,508 controls. In CAD, the overall odds ratio for carriers of the PlA2 allele was 1.10 (95% CI: 1.03 to 1.18), and it was 1.21 (95% CI: 1.05 to 1.38) in subjects younger than 60. Overall odds ratio was 1.31 (95% CI: 1.10 to 1.56) after revascularization procedures.The association of PlA2 status with overall cardiovascular disease in the general population is significant but weak; higher risk has been identified in less heterogeneous subgroups as in the younger cohorts and in the restenosis subset with stents.


2017 ◽  
Vol 16 (3) ◽  
pp. 103-103
Author(s):  
Chris Roseveare ◽  

The role of consultants in the referral process for acute medicine has been a subject of discussion for as long as I have been involved with the speciality. This journal has previously published data from individual sites which demonstrated benefits on a local level when consultants were directly involved in taking referral phone calls from general practitioners. This was further evaluated as part of the Society for Acute Medicine’s 2016 Benchmarking Audit, (SAMBA16), which generated some National data around outcomes according to the seniority of clinician receiving the referral. This is presented in the current edition. The authors acknowledge the limitations of the data, particularly the difficulty in comparing units with different facilities for assessment, treatment and follow-up, which may have influenced the options available for consultants when taking referrals. As with previous research in this area, the paper focuses on the quantitative benefits in terms of the admissions ‘avoided’ as a result of telephone advice given; the data collection does not allow any analysis of what subsequently happened to these patients, and it is possible that some were subsequently admitted to hospital. It is important also to remember the qualitative benefits of direct communication with GPs: the ability to glean important nuggets of information which may be omitted from a referral letter, as well as the value of regular conversations in building relationships between primary and secondary care. My own experiences over the past 2 decades suggest that these benefits are often at least as great, albeit more difficult to measure, than ‘admission avoidance’. Infections represent a large proportion of the acute medical intake, and this is reflected in many of the case reports we receive for consideration of publication. Three such cases are included in this edition. When the case history includes ‘visiting sewage-contaminated land’, many clinicians would be thinking along the lines of leptospirosis while awaiting serological testing. However in the case presented by Sarah Lawrence and colleagues from the Manchester area, it turned out to be the family pet which was responsible for their patient’s disseminated intravascular coagulation. Captocytophaga carnimorsis is not an organism with which I was previously familiar, but this case has reinforced my view that allowing your dog to lick your mucus membranes is something to be avoided. Lemierr’s syndrome is another condition which I have not previously encountered; however the authors of our third case report suggest this may be worth considering when a patient’s ‘simple sore throat’ fails to improve. In this case, it was the finding of another unusual bacterium – fusebacterium necrophorum – in the blood culture which led to the further investigation and diagnosis of this condition. Early recognition and initiation of appropriate antibiotic therapy is associated with an improved outcome, so this represents an important reminder of a condition which might otherwise be forgotten. Although this is technically the ‘autumn edition’, I suspect that Winter may already have arrived with a vengeance by the time it has been printed and mailed, so I hope that readers working in the NHS’ busy Acute Medical Units are managing to keep their spirits up, and have battened down the necessary hatches for whatever the months ahead choose to throw at us.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Hassan Khan ◽  
Setor Kunutsor ◽  
Jussi Kauhanen ◽  
Sudhir Kurl ◽  
Eiran Gorodeski ◽  
...  

Background: There remains uncertainty regarding the association between fasting glucose (FG) and the risk of heart failure (HF) in individuals without a history of diabetes. Methods and Results: We assessed the association between FG and HF risk in a population-based cohort of 1,740 men aged 42-61 years free from HF or diabetes at baseline. Additionally, we performed a meta-analysis of relevant prospective studies identified from MEDLINE, EMBASE, and Web of Science databases. During a mean follow-up of 20.4 years, 146 participants developed HF (4.1 cases per 1000 person-years). In models adjusted for age, the hazard ratio (HR) for HF per 1 mmol/L increase in FG was 1.34 (95% confidence interval [CI], 1.22, 1.48). This association persisted after adjustment for established HF risk factors (HR 1.27, 95% CI 1.14, 1.42). Compared with FG< 5.6 mmol/L, there was an increased risk amongst those with FG 5.6-6.9 mmol/L (HR 1.24, 95% CI 0.82, 1.88) and ≥ 7.0 mmol/L (HR 3.25, 95% CI 1.50, 7.08). HRs remained consistent across several clinical subgroups. In a meta-analysis of 10 prospective studies (Figure 1) involving a total of 4,213 incident HF cases, the HR for HF per 1 mmol/L increase in FG level was 1.11 (95% CI 1.04, 1.17), consistent with a linear dose-response relationship with evidence of heterogeneity between studies (I2=79%, 63-89%; P<0.001). Conclusions: A positive, continuous, and independent association exists between FG and risk for HF. Further studies are needed to evaluate the causal relevance of these findings.


Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 970 ◽  
Author(s):  
Gloria Ravegnini ◽  
Sarah Cargnin ◽  
Giulia Sammarini ◽  
Federica Zanotti ◽  
Justo Lorenzo Bermejo ◽  
...  

Background: A wealth of evidence has shown that microRNAs (miRNAs) can modulate specific genes, increasing our knowledge on the fine-tuning regulation of protein expression. miR-221 and miR-222 have been frequently identified as deregulated across different cancer types; however, their prognostic significance in cancer remains controversial. In view of these considerations, we performed an updated systematic review and meta-analysis of published data investigating the effects of miR-221/222 on overall survival (OS) and other secondary outcomes among cancer patients. A systematic search of PubMed, Web of Knowledge, and Cochrane Library databases was performed. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to assess the strength of association. Results: Fifty studies, analyzing 6086 patients, were included in the systematic review. Twenty-five studies for miR-221 and 17 studies for miR-222 which assessed OS were included in the meta-analysis. High expression of miR-221 and miR-222 significantly predicted poor OS (HR: 1.48, 95% CI: 1.14–1.93, p = 0.003 and HR: 1.90, 95% CI: 1.43–2.54, p < 0.001, respectively). Subgroup analysis revealed that the finding on miR-221 was not as robust as the one on miR-222. Furthermore, high miR-222 expression was also associated with worse progression-free survival and disease-free survival pooled with recurrence-free survival. Conclusions: The meta-analysis demonstrated that high expression of miR-222 is associated with poor prognosis in cancer patients, whereas the significance of miR-221 remains unclear. More work is required to fully elucidate the role of miR-221 and miR-222 in cancer prognosis, particularly in view of the limitations of existing results, including the significant heterogeneity and limited number of studies for some cancers.


2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Chitra Punjabi ◽  
Vivian Tien ◽  
Lina Meng ◽  
Stan Deresinski ◽  
Marisa Holubar

Abstract Background Using published data, we sought to compare outcomes in patients transitioned to either oral fluoroquinolones (FQs) or trimethoprim-sulfamethoxazole (TMP-SMX) vs ß-lactams (BLs) after an initial intravenous (IV) course for gram-negative rod (GNR) bacteremia. Methods We conducted a systematic review of PubMed and EMBASE and published IDWeek abstracts. We included studies that reported all-cause mortality and/or infection recurrence in patients transitioned to oral FQ/TMP-SMX and BLs. Results Eight retrospective studies met inclusion criteria with data for 2289 patients, of whom 65% were transitioned to oral FQs, 7.7% to TMP-SMX, and 27.2% to BLs. Follow-up periods ranged from 21 to 90 days. All-cause mortality was not significantly different between patients transitioned to either FQ/TMP-SMX or BLs (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.69–1.87). Overall recurrence of infection, either bacteremia or the primary site, occurred more frequently in patients transitioned to oral BLs vs FQs (OR, 2.05; 95% CI, 1.17–3.61). Analysis limited to recurrent bacteremia was similarly suggestive, although limited by small numbers (OR, 2.15; 95% CI, 0.93–4.99). However, based on known pharmacokinetics/pharmacodynamics, prescribed ß-lactam dosing regimens were frequently suboptimal. Conclusions In the step-down IV to oral treatment of GNR bacteremia, we found insufficient data regarding outcomes after oral TMP-SMX; however, selection of an FQ over commonly utilized ß-lactam regimens may reduce chances of infection recurrence. Although this may be a class effect, it may simply be the result of inadequate dosing of ß-lactams. Additional investigations are warranted to determine outcomes with TMP-SMX and optimized oral ß-lactam dosing regimens.


2020 ◽  
Vol 99 (5) ◽  
pp. 571-581 ◽  
Author(s):  
Ahmed M. Abbas ◽  
Ahmed Samy ◽  
Khaled Atwa ◽  
Hanan M. Ghoneim ◽  
Mariam Lotfy ◽  
...  

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