Association between percent decline in serum total homocysteine and risk of first stroke

Huang, Xiao; Li, Youbao; Li, Ping; Li, Jianping; Bao, Huihui; Zhang, Yan; Zhang, Yuanyuan; Sun, Ning; Wang, Ji‐Guang; He, Minqiang; Yin, Dou; Tang, Genfu; Chen, Yundai; Cui, Yong; Huang, Yining; Hou, Fan Fan; Huo, Yong; Cheng, Xiaoshu

doi:10.1212/wnl.0000000000004648

Cited by 61 publications

(48 citation statements)

References 26 publications

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“…The two recent meta‐analyses also reported that tHcy‐lowering therapy is effective in the prevention of stroke. Furthermore, it has been suggested that percent lowering in tHcy was significantly associated with a reduction in first stroke risk and may possibly serve as a useful indicator for folic acid treatment efficacy on stroke prevention . Consistently, our previous meta‐analysis suggested that there was a significant dose‐response relationship between the percent reduction of tHcy and the decrease in carotid intima‐media thickness, and a greater beneficial effect associated with folic acid therapy was seen in those trials with a larger Hcy reduction (≥30%) .…”

Section: Introductionsupporting

confidence: 74%

“…Furthermore, it has been suggested that percent lowering in tHcy was significantly associated with a reduction in first stroke risk and may possibly serve as a useful indicator for folic acid treatment efficacy on stroke prevention. 13 Consistently, our previous meta-analysis suggested that there was a significant dose-response relationship between the percent reduction of tHcy and the decrease in carotid intima-media thickness, and a greater beneficial effect associated with folic acid therapy was seen in those trials with a larger Hcy reduction (≥30%). 14 Possible mechanisms by which tHcy causes vascular damage include inhibiting endothelial cell growth, inducing endothelial dysfunction, and promoting vascular remodeling.…”

Section: Introductionsupporting

confidence: 69%

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Association between serum total homocysteine and arterial stiffness in adults: a community‐based study

Chen

Zhang

Wang

et al. 2018

J of Clinical Hypertension

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Both increased arterial stiffness and higher total homocysteine (tHcy) are associated with an elevated risk for cardiovascular disease. However, the relationship between tHcy and arterial stiffness is still inconclusive. The authors aimed to test the relationship of tHcy with carotid-femoral pulse wave velocity (cfPWV) and examine the possible effect modifiers in adults. A study was conducted from July to September 2016 in Jiangsu Province, China. A total of 16 644 participants were enrolled in the final analysis. Increased arterial stiffness is defined as a cfPWV ≥10 m/s. Overall, there was a positive association between tHcy and cfPWV levels (per 5-μmol/L tHcy increase: β = 0.10; 95% confidence interval [CI], 0.08-0.13) and increased arterial stiffness (per 5-μmol/L tHcy increase: odds ratio, 1.11; 95% CI, 1.07-1.14). Compared with participants with tHcy <10 μmol/L, the significantly higher cfPWV levels were observed in those with tHcy ≥15 μmol/L (β = 0.37; 95% CI, 0.28-0.47). Accordingly, a higher prevalence of increased arterial stiffness was found in patients with tHcy10 to <15 μmol/L (odds ratio, 1.18; 95% CI, 1.05-1.33) and tHcy ≥15 μmol/L (odds ratio, 1.50; 95% CI, 1.32-1.71) as compared with participants with tHcy <10 μmol/L. Furthermore, the stronger positive association was found in participants who were older (≥60 years, P for interaction = .008), had low body mass index (<25 kg/m , P for interaction = .026), high systolic blood pressure levels (≥145 mm Hg [median], P for interaction = .048), or diabetes mellitus (P for interaction = .045). The present study demonstrated that serum tHcy concentrations were positively associated with cfPWV and the prevalence of increased arterial stiffness. These results suggest that the cardiovascular effects of tHcy may partly be mediated through arterial stiffness.

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Section: Introductionsupporting

confidence: 74%

Section: Introductionsupporting

confidence: 69%

Association between serum total homocysteine and arterial stiffness in adults: a community‐based study

Chen

Zhang

Wang

et al. 2018

J of Clinical Hypertension

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“…Furthermore, a significant positive dose-response association has been found between degree of tHcy reduction and systolic blood pressure (SBP) reduction (6) , and decrease in CVD (7) or carotid intima-media thickness (8) . Consistently, a recent study found that the lowering of tHcy was significantly associated with a reduction in first stroke risk, and may possibly serve as a useful indicator for the use of folic acid therapy in the prevention of stroke (9) .…”

supporting

confidence: 56%

Effect of long-term low-dose folic acid supplementation on degree of total homocysteine-lowering: major effect modifiers

Zhang

et al. 2018

Br J Nutr

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We sought to examine the potential modifiers in the association between long-term low-dose folic acid supplementation and the reduction of serum total homocysteine (tHcy) among hypertensive patients, using data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 16 867 participants who had complete data on tHcy measurements at both the baseline and exit visit. After a median treatment period of 4·5 years, folic acid treatment significantly reduced the tHcy levels by 1·6 μmol/l (95 % CI 1·4, 1·8). More importantly, after adjustment for baseline tHcy and other important covariates, a greater degree of tHcy reduction was observed in certain subgroups: males, the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, higher baseline tHcy levels (≥12·5 (median) v. <12·5 μmol/l), lower folate levels (<8·0 (median) v. ≥8·0 ng/ml), estimated glomerular filtration rate (eGFR) <60 ml/min per 1·73 m2 (v. 60–<90 and ≥90 ml/min per 1·73 m2), ever smokers and concomitant use of diuretics (P for all interactions <0·05). The degree of tHcy reduction associated with long-term folic acid supplementation can be significantly affected by sex, MTHFR C677T genotypes, baseline folate, tHcy, eGFR levels and smoking status.

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“…41 A recent meta-analysis has concluded that serum homocysteine levels are elevated in patients with BD even during the euthymic state. 47 In our study, the mean serum levels of homocysteine in either LOBD or EOBD group were actually above 11 umol/L and therefore may account for the link to cognitive dysfunctions. In the studies of elderly general population, the serum levels of homocysteine over 11 umol/L were found to be associated with the increased risk of dementia and atrophy of medial temporal lobe.…”

Section: Discussionmentioning

confidence: 39%

“…43,44 The elevated levels of homocysteine potentially lead to cognitive dysfunctions due to the activations of inflammatory and oxidative stress pathways or the reactivations of cholinergic metabolism 45,46 as well as being a potential vascular risk factor itself. 47 In our study, the mean serum levels of homocysteine in either LOBD or EOBD group were actually above 11 umol/L and therefore may account for the link to cognitive dysfunctions.…”

Section: Discussionmentioning

confidence: 39%

Homocysteine, rather than age of onset, is a better predictor for cognitive function in older adults with bipolar disorder

Chen

Liu

et al. 2019

Int J Geriat Psychiatry

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Objectives The association between older‐age bipolar disorder and cognitive impairments may be mediated by vascular burden. The aim of the study was to examine the difference of cognitive function between older people with late‐onset bipolar disorder (LOBD) and early‐onset bipolar disorder (EOBD) by considering rigorous vascular risk burden evaluation, comprehensive cognitive tests, and relevant biochemistry data. Methods We recruited 95 outpatients aged over 55 with a DSM‐IV‐TR diagnosis of bipolar I disorder. Fifty had LOBD, defined by age of onset after 40. Cognitive function was evaluated through a battery of tests assessing verbal memory, attention/speed, visuospatial function, verbal fluency, and cognitive flexibility. Vascular risk assessments included individual disorders, 10‐year Framingham cardiovascular risk scores, and serum levels of homocysteine, vitamin B12, folate, and triiodothyronine. Results No differences were observed between LOBD and EOBD on any cognitive test after adjusting for potential confounders. In addition to age and educational years, multiple linear regression analyses indicated significantly negative associations between serum homocysteine levels and cognitive performances in attention, psychomotor speed, verbal memory, and executive function. Conclusions Among older people with bipolar disorder, LOBD is not associated with more cognitive dysfunction in this study. However, higher serum homocysteine levels were significantly associated with worse cognitive performance in this particular group. Clinicians therefore have to pay attention to the cognitive function in older bipolar patients with higher levels of homocysteine.

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Association between percent decline in serum total homocysteine and risk of first stroke

Abstract: NCT00794885.

Cited by 61 publications

References 26 publications

Association between serum total homocysteine and arterial stiffness in adults: a community‐based study

Association between serum total homocysteine and arterial stiffness in adults: a community‐based study

Effect of long-term low-dose folic acid supplementation on degree of total homocysteine-lowering: major effect modifiers

Homocysteine, rather than age of onset, is a better predictor for cognitive function in older adults with bipolar disorder

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