High plasma homocysteine levels contribute to the risk of stroke recurrence and all-cause mortality in a large prospective stroke population

2009 ◽  
Vol 118 (3) ◽  
pp. 187-194 ◽  
Author(s):  
Weili Zhang ◽  
Kai Sun ◽  
Jinxing Chen ◽  
Yuhua Liao ◽  
Qin Qin ◽  
...  

Plasma homocysteine concentrations have been associated with the risk of stroke, but its relevance to secondary vascular events and mortality after stroke remains unclear because of inconsistent results from clinical trials. The aim of the present study was to investigate whether plasma homocysteine levels and the MTHFR (methylenetetrahydrofolate reductase) variant C677T contributed to the risk of stroke recurrence and all-cause mortality in a large prospective cohort of stroke patients in a Chinese population. A total of 1823 stroke patients (age, 35–74 years) were recruited during 2000–2001 and prospectively followed-up for a median of 4.5 years. During the follow-up, 347 recurrent strokes and 323 deaths from all-causes were documented. After adjustment for age, gender and other cardiovascular risk factors, a high homocysteine concentration was associated with an increased risk of 1.74-fold for stroke recurrence {RR (relative risk), 1.74 [95% CI (confidence interval), 1.3–2.3]; P<0.0001} and 1.75-fold for all-cause mortality [RR, 1.75 (95% CI, 1.3–2.4); P<0.0001] when highest and lowest categories were compared. Spline regression analyses revealed a threshold level of homocysteine for stroke recurrence. By dichotomizing homocysteine concentrations, the RRs were 1.31 (95% CI, 1.10–1.61; P=0.016) for stroke recurrence and 1.47 (95% CI, 1.15–1.88; P<0.0001) for all-cause mortality in patients with homocysteine levels ≥16 μmol/l relative to those with levels <16 μmol/l. The association of elevated plasma homocysteine concentrations with all-cause mortality was mainly due to an increased risk of cardiovascular deaths. No significant association was found between MTHFR C677T and stroke recurrence or mortality. In conclusion, our findings suggest that elevated homocysteine concentrations can predict the risk of stroke recurrence and mortality in patients with stroke.

2020 ◽  
Vol 13 ◽  
pp. 175628642097189
Author(s):  
Clare Lambert ◽  
Durgesh Chaudhary ◽  
Oluwaseyi Olulana ◽  
Shima Shahjouei ◽  
Venkatesh Avula ◽  
...  

Background: Several studies suggest women may be disproportionately affected by poorer stroke outcomes than men. This study aims to investigate whether women have a higher risk of all-cause mortality and recurrence after an ischemic stroke than men in a rural population in central Pennsylvania, United States. Methods: We analyzed consecutive ischemic stroke patients captured in the Geisinger NeuroScience Ischemic Stroke research database from 2004 to 2019. Kaplan–Meier (KM) estimator curves stratified by gender and age were used to plot survival probabilities and Cox Proportional Hazards Ratios were used to analyze outcomes of all-cause mortality and the composite outcome of ischemic stroke recurrence or death. Fine–Gray Competing Risk models were used for the outcome of recurrent ischemic stroke, with death as the competing risk. Two models were generated; Model 1 was adjusted by data-driven associated health factors, and Model 2 was adjusted by traditional vascular risk factors. Results: Among 8900 adult ischemic stroke patients [median age of 71.6 (interquartile range: 61.1–81.2) years and 48% women], women had a higher crude all-cause mortality. The KM curves demonstrated a 63.3% survival in women compared with a 65.7% survival in men ( p = 0.003) at 5 years; however, the survival difference was not present after controlling for covariates, including age, atrial fibrillation or flutter, myocardial infarction, diabetes mellitus, dyslipidemia, heart failure, chronic lung diseases, rheumatic disease, chronic kidney disease, neoplasm, peripheral vascular disease, past ischemic stroke, past hemorrhagic stroke, and depression. There was no adjusted or unadjusted sex difference in terms of recurrent ischemic stroke or composite outcome. Conclusion: Sex was not an independent risk factor for all-cause mortality and ischemic stroke recurrence in the rural population in central Pennsylvania.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Meng ◽  
Shaoyan Huang ◽  
Yali Yang ◽  
Xiaofeng He ◽  
Liping Fei ◽  
...  

Background: Since the 1990s, there have been a lot of research on single-nucleotide polymorphism (SNP) and different diseases, including many studies on 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and essential hypertension (EH). Nevertheless, their conclusions were controversial. So far, six previous meta-analyses discussed the internal relationship between the MTHFR polymorphism and EH, respectively. However, they did not evaluate the credibility of the positive associations. To build on previous meta-analyses, we updated the literature by including previously included papers as well as nine new articles, improved the inclusion criteria by also considering the quality of the papers, and applied new statistical techniques to assess the observed associations. Objectives: This study aims to explore the degree of risk correlation between two MTHFR polymorphisms and EH. Methods: PubMed, EMBASE, the Cochrane Library, CNKI, and Wan Fang electronic databases were searched to identify relevant studies. We evaluated the relation between the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms and EH by calculating the odds ratios (OR) as well as 95% confidence intervals (CI). Here we used subgroup analysis, sensitivity analysis, cumulative meta-analysis, assessment of publication bias, meta-regression meta, False-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and Venice criterion. Results: Overall, harboring the variant of MTHFR C677T was associated with an increased risk of EH in the overall populations, East Asians, Southeast Asians, South Asians, Caucasians/Europeans, and Africans. After the sensitivity analysis, positive results were found only in the overall population (TT vs. CC: OR = 1.14, 95% CI: 1.00–1.30, Ph = 0.032, I2 = 39.8%; TT + TC vs. CC: OR = 1.15, 95% CI: 1.01–1.29, Ph = 0.040, I2 = 38.1%; T vs. C: OR = 1.14, 95% CI: 1.04–1.25, Ph = 0.005, I2 = 50.2%) and Asian population (TC vs. CC: OR = 1.14, 95% CI: 1.01–1.28, Ph = 0.265, I2 = 16.8%; TT + TC vs. CC: OR = 1.17, 95% CI: 1.04–1.30, Ph = 0.105, I2 = 32.9%; T vs. C: OR = 1.10, 95% CI: 1.02–1.19, Ph = 0.018, I2 = 48.6%). However, after further statistical assessment by FPRP, BFDP, and Venice criteria, the positive associations reported here could be deemed to be false-positives and present only weak evidence for a causal relationship. In addition, when we performed pooled analysis and sensitivity analysis on MTHFR A1298C; all the results were negative. Conclusion: The positive relationships between MTHFR C677T and A1298C polymorphisms with the susceptibility to present with hypertension were not robust enough to withstand statistical interrogation by FPRP, BFDP, and Venice criteria. Therefore, these SNPs are probably not important in EH etiology.


2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Bo Yu ◽  
Ping Yang ◽  
Xuebi Xu ◽  
Lufei Shao

Abstract Studies on the association of C-reactive protein (CRP) with all-cause mortality in acute ischemic stroke patients have yielded conflicting results. The objective of this meta-analysis was to evaluate the prognostic value of CRP elevation in predicting all-cause mortality amongst patients with acute ischemic stroke. We searched the original observational studies that evaluated the association of CRP elevation with all-cause mortality in patients with acute ischemic stroke using PubMed and Embase databases until 20 January 2018. Pooled multivariate-adjusted hazard ratio (HR) with 95% confidence intervals (CI) of all-cause mortality was obtained for the highest compared with the lowest CRP level or per unit increment CRP level. A total of 3604 patients with acute ischemic stroke from eight studies were identified. Acute ischemic stroke patients with the highest CRP level were independently associated with an increased risk of all-cause mortality (HR: 2.07; 95% CI: 1.60–2.68) compared with the lowest CRP category. The pooled HR of all-cause mortality was 2.40 (95% CI: 1.10–5.21) for per unit increase in log-transformed CRP. Elevated circulating CRP level is associated with the increased risk of all-cause mortality in acute ischemic stroke patients. This meta-analysis supports the routine use of CRP for the death risk stratification in such patients.


2020 ◽  
pp. 1-12
Author(s):  
Dimitra Liapi ◽  
Aikaterini Sfiridaki ◽  
Aikaterini Livadiotaki ◽  
Athanasios Alegakis ◽  
Kostas Stylianou ◽  
...  

<b><i>Background:</i></b> The inherited thrombophilic mutations of the factor V gene (FVG1691A Leiden-FVL), prothrombin gene (PTG20210A), and the methylenetetrahydrofolate reductase gene C677T (MTHFR C677T) are risk factors for thromboembolic events and are related to the pathogenesis of vascular diseases. <b><i>Objectives:</i></b> The main objective of this study was to explore the role of these factors in the pathogenesis of chronic kidney disease (CKD) and survival of patients with CKD-5 receiving haemodialysis. <b><i>Methods:</i></b> A cohort of 395 patients with CKD-5 on haemodialysis, from 6 dialysis units in Crete, Greece were recruited based on their medical records and were followed for 5 years. We collected data on CKD-5 aetiology, thrombophilic gene expression, vascular access thrombosis, time of death, and causes of death. <b><i>Results:</i></b> The mutated genes just as prevalent in patients with CKD-5 as they were in a control group with no renal disease (<i>p</i> &#x3e; 0.05). FVL heterozygosity was significantly more prevalent (11.4 vs. 5.7%; <i>p</i> = 0.036) in patients presented with CKD of unknown aetiology, compared to CKD secondary to known aetiologies. The survival of patients with CKD-5 receiving haemodialysis was not affected by the presence of any thrombophilic mutation. This held true for the whole cohort and for the cohort that included only lethal vascular events. Most patients with MTHFR C677T heterozygosity, and all patients with MTHFR C677T homozygosity, died from vascular events during the follow-up period. <b><i>Conclusion:</i></b> The FVL mutation may act as a risk factor for CKD. This study increases our understanding of molecular mechanisms in the pathogenesis of CKD of unknown aetiology. Τhe presence of thrombophilic mutations did not affect the overall survival of patients with CKD-5. This finding probably reflects the effect of medical care on patient outcomes.


2020 ◽  
Author(s):  
Siya Kong ◽  
Feng Ye ◽  
Yini Dang ◽  
Yifei Hua ◽  
Guoxin Zhang

Abstract Background Previous reports indicate that the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism plays a role in gastric cancer. However, whether it influences the development and progression of atrophic gastritis remains unclear. We aim to determine the possible association between the MTHFR 677C > T polymorphism and the severity of atrophic gastritis. Methods A total 128 patients with atrophic gastritis were included in the study. The presence and severity of gastric atrophy was assessed by histology using OLGA and OLGIM Gastritis Staging System. MTHFR 677C > T genotyping was performed by digital fluorescence molecular hybridization. Categorical variables were analyzed by percentages using the χ2 test. Results In this study, the TT genotype was significantly more frequent among patients aged ≤ 44 years (age ≤ 44 years vs. >44 years, P = 0.039). Patients with the TT genotype showed a higher ratio of incisura with atrophy or intestinal metaplasia (TT vs. CC + CT, P = 0.02). Furthermore, the TT genotype was associated with more severe lesions compared with the CC + CT genotypes (TT vs. CC + CT for atrophy: odds ratio [OR] = 2.18, P = 0.07; for intestinal metaplasia: OR = 3.39, P = 0.02; for moderate-to-severe lesions: OR = 3.84, P = 0.02). OLGA and OLGIM stages III-IV were observed more frequently in patients with the TT genotype compared with the CC + CT genotypes (for OLGA: OR = 3.98, P = 0.004; for OLGIM: OR = 2.45, P = 0.04). Conclusions The MTHFR 677C > T TT genotype showed an increased risk of moderate-to-severe lesions by OLGA and OLGIM stages, and these results suggest that the MTHFR C677T polymorphism may serve as a predictive marker for precancerous gastric lesions, especially in patients aged ≤ 44 years.


2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Yu Fan ◽  
Menglin Jiang ◽  
Dandan Gong ◽  
Changfeng Man ◽  
Yuehua Chen

Cardiac troponins are specific biomarkers of cardiac injury. However, the prognostic usefulness of cardiac troponin in patients with acute ischemic stroke is still controversial. The objective of this meta-analysis was to investigate the association of cardiac troponin elevation with all-cause mortality in patients with acute ischemic stroke. PubMed and Embase databases were searched for relevant studies up to April 31, 2017. All observational studies reporting an association of baseline cardiac troponin-T (cTnT) or troponin-I (cTnI) elevation with all-cause mortality risk in patients with acute ischemic stroke were included. Pooled adjusted risk ratio (RR) and corresponding 95% confidence interval (CI) were obtained using a random effect model. Twelve studies involving 7905 acute ischemic stroke patients met our inclusion criteria. From the overall pooled analysis, patients with elevated cardiac troponin were significantly associated with increased risk of all-cause mortality (RR: 2.53; 95% CI: 1.83–3.50). The prognostic value of cardiac troponin elevation on all-cause mortality risk was stronger (RR: 3.54; 95% CI: 2.09–5.98) during in-hospital stay. Further stratified analysis showed elevated cTnT (RR: 2.36; 95% CI: 1.47–3.77) and cTnI (RR: 2.79; 95% CI: 1.68–4.64) level conferred the similar prognostic value of all-cause mortality. Acute ischemic stroke patients with elevated cTnT or cTnI at baseline independently predicted an increased risk of all-cause mortality. Determination of cardiac troponin on admission may aid in the early death risk stratification in these patients.


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