Hyperhomocysteinemia and Ischemic Stroke: A Potential Dose-Response Association—A Systematic Review and Meta-analysis

Holmen, Marte; Hvas, Anne‐Mette; Arendt, Johan Frederik Håkonsen

doi:10.1055/s-0041-1735978

Cited by 19 publications

(15 citation statements)

References 106 publications

(277 reference statements)

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Section: Accepted Manuscriptmentioning

confidence: 99%

“…58 Another meta-analysis showed a dose-response of the risk association of t-Hcy with ischemic stroke with a 43% increased risk per 5 µmol/L increase in t-Hcy level. 59 A third meta-analysis of 10 prospective studies found a pooled relative risk at 1.06 for stroke and 1.05 for ischemic stroke for each 1 µmol/L increase of t-Hcy. 60 Despite these multiple sources of evidence, it is noteworthy that a very limited interest was directed to patients with intermediate and major HHcy.…”

Section: Observational Evidence Of the Dose-effect Association Of Hom...mentioning

confidence: 99%

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Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

et al. 2022

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Thromboembolic manifestations are relativement frequent in patients with intermediate/severe hyperhomocysteinemia (> 30 µmol/L) related to inherited disorders and deficiencies in vitamin B12 and folate. In contrast, moderate hyperhomocysteinemia (15- 30 µmol/L) is a modest predictor of cardiovascular risk. The recognition of homocysteine as a cardiovascular risk factor has been challenged by some but not all randomized clinical trials. We reviewed the main data of this controversy and formulated conclusions to be translated in clinical practice. Lowering homocysteine trials have been performed in cardiovascular subjects with moderate but not intermediate/severe hyperhomocysteinemia despite the dose-effect risk association. The first meta-analyses found no benefit and led cardiology societies not recommending homocysteine in the assessment of cardiovascular risk. This guideline challenged the need to diagnose and treat the nutritional and genetic causes of intermediate/major hyperhomocysteinemia and was not revised when larger meta-analyses concluded to a reduced risk of stroke. In a recent observational study, 84% of consecutive cardiovascular patients assessed for homocysteine had intermediate or major hyperhomocysteinemia, which was properly assessed in only half cases and related to B12 and/or folate deficiency and Addisson/Biermer disease in 55% of these cases. In conclusion, revisiting observational studies and clinical trials suggests that cardiovascular patients should be screened for hyperhomocysteinemia, when no other risk factor is found. Patients with intermediate/major hyperhomocysteinemia should be properly assessed and treated for vitamin B deficiencies and inherited disorders according to current guidelines. Further trials are needed to assess the lowering homocysteine effect according to hyperhomocysteinemia categories at baseline.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Observational Evidence Of the Dose-effect Association Of Hom...mentioning

confidence: 99%

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

et al. 2022

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“…Elevated HCY could promote oxygen free radical generation and damage the vascular endothelium leading to platelet aggregation and thrombosis ( 37 ). Furthermore, a meta-analysis indicated that a non-linear association could exist between HCY levels and risk of IS ( 38 ). Therefore, we analyzed the correlation between HCY levels and CR, and confirmed that high HCY levels significantly correlated to CR (OR 1.209; 95% CI 1.072–1.362; p = 0.002), which was consistent with another study ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of CYP2C19 gene polymorphism and influencing factors of pharmacological response of clopidogrel in patients with cerebral infarction in Zhejiang, China

Lu²,

Guo³

et al. 2023

Front. Cardiovasc. Med.

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BackgroundCertain genetic and non-genetic factors may cause damaged platelet inhibition by clopidogrel. We aimed to determine the effect of cytochrome P4502C19 (CYP2C19) polymorphism, along with other clinical factors, on the platelet response to clopidogrel in patients with acute ischemic stroke (AIS).MethodsA total of 214 patients with AIS receiving clopidogrel at a maintenance dose of 75 mg daily admitted to the Ningbo First Hospital between 1 January 2020, and 31 December 2021, were enrolled. Platelet aggregation analysis was performed to determine clopidogrel resistance. Quantitative real-time polymerase chain reaction (QRT-PCR) was used to determine CYP2C19 genotype. Other laboratory data on complete blood count and biochemical parameters were taken from patient medical files.ResultsAmong the 214 AIS patients treated with clopidogrel in the Ningbo population, the incidence of clopidogrel resistance was approximately 43.9%, and the distribution of CYP2C19 genotypes was highest for CYP2C19(*1/*2) (43.0%), followed by CYP2C19 (*1/*1) (38.8%). The distribution of alleles *1, *2, *3, and *17 was 62.1, 32.5, 4.9, and 0.5%, respectively. A chi-squared test showed that the gene frequencies of alleles *2 and *3 were significantly higher in the clopidogrel-resistant group than in the clopidogrel-sensitive group (p < 0.001), and a Mann–Whitney U-test showed that high HCY levels were significantly correlated with clopidogrel resistance (p < 0.001). Multi-factor logistic regression analysis demonstrated that mutant heterozygous genotype [OR 2.893; 95% confidence interval (CI) 1.456–5.748; p = 0.002], mutant homozygous genotype (OR 4.741; 95% CI 1.828–12.298; p = 0.001), and high HCY levels (OR 1.209; 95% CI 1.072–1.362; p = 0.002) were significantly associated with clopidogrel resistance.ConclusionAccording to our results, carrying the CYP2C19*2/*3 allele and high HCY levels are independent risk factors for clopidogrel resistance after clopidogrel therapy in patients with AIS. These two factors should be considered prior to clopidogrel administration.

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“…Гомоцистеин -интегративный показатель эндотелиальной дисфункции, доступный в рутинной клинической практике [26,27]. Ранее были опубликованы работы, указываю щие на вклад гипергомоцистеинемии в замедление вестибулярной реабилитации после перенесенного вестибулярного нейронита [28], а также ухудшение показателей постуральной устойчивости [29].…”

Section: гомоцистеинunclassified

Vitamin D and homocysteine in benign paroxysmal positional vertigo

Bedenko

Антоненко

2022

Medicinskij sovet

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Introduction. Benign paroxysmal positional vertigo (BPPV) is one of the most common causes of vertigo. Among the possible pathophysiological concepts, the largest evidence to date has been collected on the relationship of BPPV with a lack of vitamin D. Few studies have also been published on the assessment of factors of endothelial dysfunction (and, as a result, disturbances in the microcirculation of the inner ear) and BPPV. The problems of metabolic disorders in BPPV were still poorly highlighted in Russian sources.Objective. To investigate the levels of 25-OH-vitamin D and homocysteine among patients with BPPV and compare these factors depending on recurrence.Materials and methods. The study included 53 patients with BPPV, age 60 ± 12.6 (Me 62 [55; 68]), men accounted for 24.5%, women – 75.5%. All patients underwent a study of the neurological status and neurovestibularexamination, which included the Halmagi test, the head shake test, the Fukuda test, the Dix – Hallpike and McClure – Pagnini tests. Plasma 25-OH-vitamin D and homocysteine levels were assessed using enzyme-linked immunosorbent assay. The severity of vertigo was assessed using the dizziness handicap inventory (DHI).Results. The level of 25-OH vitamin D in with BPPV varied from 5.2 to 40 ng/ml, the average value was 19.53 ± 9.07 ng/ml, which corresponds to the deficit according to international recommendations (Me 17 [13; 24.8]). The level of 25-OH vitamin D in the group with recurrent BPPV was (Me 15 [12 and 22]), which was significantly lower than in the group with a single BPPV episode. The DHI score was significantly lower in the group with recurrent BPPV. There was a negative relationship between 25-OH-vitamin D levels and age, and a negative relationship between 25-OH-vitamin D and homocysteine in the DPPV group.Conclusion. There was a decrease in the level of 25-OH-vitamin D among patients with BPPV; in the group with recurrent BPPV, the level of 25-OH-vitamin D was significantly lower than in the group with a single dose of BPPV. The presence of an inverse correlation between the level of homocysteine and 25-OH-vitamin D indicates the advisability of more detailed studies of the potential contribution of endothelial dysfunction to the development of peripheral vestibular disorders due to impaired microcirculation of the otoconial apparatus.

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Hyperhomocysteinemia and Ischemic Stroke: A Potential Dose-Response Association—A Systematic Review and Meta-analysis

Cited by 19 publications

References 106 publications

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

Analysis of CYP2C19 gene polymorphism and influencing factors of pharmacological response of clopidogrel in patients with cerebral infarction in Zhejiang, China

Vitamin D and homocysteine in benign paroxysmal positional vertigo

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