Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men

Zhou, Ziyi; Li, Jianping; Yu, Yigang; Li, Youbao; Zhang, Yan; Liu, Lishun; Song, Yun; Zhao, Min; Wang, Yu; Tang, Genfu; He, Minqiang; Xu, Xiping; Cai, Yefeng; Dong, Qiang; Yin, Dou; Huang, Xiao; Cheng, Xiaoshu; Zhang, Yuanyuan; Hou, Fan Fan; Wang, Xiaobin; Huo, Yong

doi:10.1161/strokeaha.117.018273

Cited by 14 publications

(14 citation statements)

References 25 publications

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“…Notably, potential associations with negative health outcomes, such as augmenting cancer and influencing insulin resistance, have led to a growing controversy about the current use of folic acid as a food supplement (Choi et al, 2014 ; Lucock & Yates, 2009 ; Maruvada et al, 2020 ). In addition, the dosing needed and effectiveness of folic acid as a therapy for cardiovascular diseases have been inconsistent (Shirodaria et al, 2007 ; Zhou et al, 2018 ). Thus, there is growing awareness of the need for more research to assess the health effects of using folic acid in amounts exceeding current recommendations for upper limits (Field & Stover, 2018 ; Maruvada et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Folic acid, either solely or combined with L‐citrulline, improves NO signaling and ameliorates chronic hypoxia‐induced pulmonary hypertension in newborn pigs

Douglass

Dikalova

Kaplowitz

et al. 2021

Physiological Reports

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Concomitant with developing pulmonary hypertension (PH), newborn piglets exposed to chronic hypoxia develop pulmonary vascular NO signaling impairments. PH is reduced and NO signaling is improved in chronically hypoxic piglets treated with the NO‐arginine precursor, L‐citrulline. Folic acid positively impacts NO signaling. We evaluated whether the effect on NO signaling and PH is greater using co‐treatment with folic acid and L‐citrulline than either alone. From day 3 to day 10 of hypoxia, piglets were treated solely with folic acid, solely with L‐citrulline, or co‐treated with both. Catheters were placed to measure in vivo hemodynamics. NO production was measured in vitro in dissected pulmonary arteries. Compared to normoxic piglets, pulmonary vascular resistance (PVR) was elevated and NO production was reduced in untreated hypoxic piglets. Regardless of treatment strategy, PVR was less in all three treated groups of hypoxic piglets when compared to the untreated hypoxic group. In addition, for all three groups of treated hypoxic piglets, NO production was higher than the untreated group. Improvements in PVR and NO production did not differ between piglets co‐treated with folic acid and L‐citrulline and those treated solely with either. Thus, the impact on NO production and PVR was not augmented by combining folic acid and L‐citrulline treatments. Nonetheless, treatment with folic acid, either singly or when combined with L‐citrulline, increases NO production and inhibits PH in chronically hypoxic newborn piglets. Folic acid merits consideration as a therapy for PH in human infants with chronic heart and lung conditions that are associated with chronic hypoxia.

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Section: Discussionmentioning

confidence: 99%

Folic acid, either solely or combined with L‐citrulline, improves NO signaling and ameliorates chronic hypoxia‐induced pulmonary hypertension in newborn pigs

Douglass

Dikalova

Kaplowitz

et al. 2021

Physiological Reports

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“…Cigarette smoke, which contains thiocyanate, and cigarette smoking, which has been associated with lower folate and higher tHcy concentrations than never smokers, may also attenuate the effect of folic acid in preventing stroke. 41 A subgroup analysis from the CSPPT reported that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect of folic acid therapy on preventing stroke. 41 …”

Section: Evidence For Homocysteine As a Causal Risk Factor For Strokementioning

confidence: 99%

“… 41 A subgroup analysis from the CSPPT reported that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect of folic acid therapy on preventing stroke. 41 …”

Section: Evidence For Homocysteine As a Causal Risk Factor For Strokementioning

confidence: 99%

B vitamins for stroke prevention

Hankey

2018

Stroke Vasc Neurol

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Supplementation with B vitamins (vitamin B9(folic acid), vitamin B12 and vitamin B6) lowers blood total homocysteine (tHcy) concentrations by about 25% and reduces the relative risk of stroke overall by about 10% (risk ratio (RR) 0.90, 95% CI 0.82 to 0.99) compared with placebo. Homocysteine-lowering interventions have no significant effect on myocardial infarction, death from any cause or adverse outcomes. Factors that appear to modify the effect of B vitamins on stroke risk include low folic acid status, high tHcy, high cyanocobalamin dose in patients with impaired renal function and concurrent antiplatelet therapy. In regions with increasing levels or established policies of population folate supplementation, evidence from observational genetic epidemiological studies and randomised controlled clinical trials is concordant in suggesting an absence of benefit from lowering of homocysteine with folic acid for prevention of stroke. Clinical trials indicate that in countries which mandate folic acid fortification of food, folic acid supplementation has no significant effect on reducing stroke risk (RR 1.05, 95% CI 0.90 to 1.23). However, in countries without mandatory folic acid food fortification, folic acid supplementation reduces the risk of stroke by about 15% (RR 0.85, 95% CI 0.77 to 0.94). Folic acid alone or in combination with minimal cyanocobalamin (≤0.05 mg/day) is associated with an even greater reduction in risk of future stroke by 25% (RR 0.75, 95% CI 0.66 to 0.86), whereas the combination of folic acid and a higher dose of cyanocobalamin (≥0.4 mg/day) is not associated with a reduced risk of future stroke (RR 0.95, 95% CI 0.86 to 1.05). The lack of benefit of folic acid plus higher doses of cyanocobalamin (≥0.4 mg/day) was observed in trials which all included participants with chronic kidney disease. Because metabolic B12 deficiency is very common and usually not diagnosed, future randomised trials of homocysteine-lowering interventions for stroke prevention should probably test a combination of folic acid and methylcobalamin or hydroxocobalamin instead of cyanocobalamin, and perhaps vitamin B6.

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“…This could be exacerbated by loss of B vitamin and folate during dialysis. Moreover, the elevated levels of homocysteine could be reduced by the folic acid supplementation, which could modify stroke in Chinese hypertensive patients 26 . Therefore, dietary intervention might help to reduce the risk of CVD.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Predialysis Systolic Blood Pressure Variability and Intradialytic Cardiac Hemodynamics in Hemodialysis Patients

Yang

Huang

et al. 2020

Preprint

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The association in hemodialysis patients between long-term predialysis blood pressure variability and intradialytic cardiac hemodynamics was assessed prospectively in 1070 patients receiving maintenance hemodialysis for more than 3 months. Predialysis blood pressure variability was assessed over 1-year intervals. Outcomes included factors were intradialytic hypotension and change in rate-pressure product. The final cohort’s mean age was 59 years, and 57% were males. Greater predialysis systolic blood pressure variability was associated with an increased risk of intradialytic hypotension (adjusted hazard ratio, 1.097; 95% confidence intervals 1.055 to 1.140) and change in rate-pressure product (adjusted hazard ratio, 1.213; 95% confidence intervals 1.163 to 1.265). Results were similar when blood pressure variability was stratified by baseline systolic blood pressure. Factors associated with higher systolic blood pressure variability were older age, female sex, longer duration of dialysis, and diagnosis of diabetic nephropathy, and lower levels of serum albumin. In conclusion, greater predialysis systolic blood pressure variability among hemodialysis patients was associated with greater intradialytic cardiac hemodynamic instability. Strategies to reduce blood pressure variability might be beneficial for hemodialysis patients.

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Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men

Abstract: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Cited by 14 publications

References 25 publications

Folic acid, either solely or combined with L‐citrulline, improves NO signaling and ameliorates chronic hypoxia‐induced pulmonary hypertension in newborn pigs

Folic acid, either solely or combined with L‐citrulline, improves NO signaling and ameliorates chronic hypoxia‐induced pulmonary hypertension in newborn pigs

B vitamins for stroke prevention

Long-Term Predialysis Systolic Blood Pressure Variability and Intradialytic Cardiac Hemodynamics in Hemodialysis Patients

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