Study identifies biomarker to measure benefits of folic acid on stroke prevention

October 27, 2017, European Society of Cardiology

An analysis of the China Stroke Primary Prevention Trial presented at the 28th Great Wall International Congress of Cardiology (GW-ICC) and published in Neurology has identified a biomarker that can be used to measure the benefits of folic acid supplementation on stroke prevention.

"Stroke is the leading cause of death and adult disability in China, and incidence is increasing at an annual rate of 8.3 percent," said lead author Dr Xiao Huang, attending physician, Department of Cardiology, Second Affiliated Hospital of Nanchang University, Jiangxi Province, China. "Around 2 percent of Chinese adults aged 40 years and older have had a stroke."

Hypertension affects 25.2 percent of people aged 18 and above in China and is the primary risk factor for stroke, especially when accompanied by elevated . Dietary folate is the most important determinant of homocysteine.

The China Stroke Primary Prevention Trial (CSPPT) previously showed that enalapril (an anti-hypertensive drug) combined with , compared to enalapril alone, significantly reduced the risk of first stroke in adults with hypertension by 21 percent during a median treatment duration of 4.5 years.

The current post-hoc analysis of the CSPPT is the first to examine whether, and to what degree, a reduction in homocysteine level was associated with the risk of first stroke in the setting of a large randomised folic acid trial.

The CSPPT was a randomised, double-blind clinical trial conducted from May 2008 to August 2013 in 32 communities in China. The trial included 20 702 men and women aged 45 to 75 years with hypertension and no history of stroke or myocardial infarction. Participants were randomly assigned, in a 1:1 ratio, to enalapril plus folic acid or enalapril alone.

This current report included 16 867 participants with homocysteine measurements at the start and end of the trial. Over a median treatment duration of 4.5 years, stroke occurred in 445 participants. Those with stroke had a significantly lower percent decline in homocysteine. A 20 percent homocysteine decline was associated with a 7 percent reduction in stroke risk (hazard ratio [HR], 0.93; 95 percent confidence interval [CI], 0.90–0.97). When percent decline in homocysteine was assessed in tertiles, a significantly lower stroke risk was found in those in tertiles 2 and 3 (HR, 0.79; 95 percent CI, 0.64–0.97) compared to the tertile .

Stratified analyses were performed to assess whether the association between percent decline in homocysteine and stroke risk differed by subgroups. None of the stratification variables, including age (<60 vs. ≥60 years), sex, treatment group, MTHFR C677T genotypes, serum folate (<8 [median] vs. ≥8 ng/ml), homocysteine levels (<12.5 [median] vs. ≥12.5 μmol/L), and time-averaged blood pressure during treatment (<140/90 vs. ≥140/90 mmHg), showed evidence of effect modification.

Dr Huang said: "Our study found that the percent decline in homocysteine was significantly associated with stroke risk in hypertensive patients in a dose-response manner. Specifically, the greater percentage of homocysteine decline, the greater reduction in stroke risk."

She concluded: "If further confirmed, homocysteine percent decline may be a useful biomarker for assessing the beneficial effect of folic acid therapy in the primary prevention of stroke. In the case of inadequate homocysteine decline, it may prompt evaluation of potential underlying reasons, such as poor adherence, insufficient folic acid dosage, or other causes of high homocysteine."

Professor Xiaoshu Cheng, the 28th GW-ICC Scientific Committee Chairman and Professor Yong Huo, the 28th GW-ICC Co-Chairman, said: "This study represents an important step towards precision prevention of stroke. It strives to use a molecular biomarker to evaluate the efficacy of folic acid therapy, which helps to better recognise individual variability in response to the intervention, and guide further personalised prevention strategies for stroke."

Professor Michel Komajda, a past president of the ESC and course director of the ESC programme in China, said: "Stroke is a major cause of disability and death worldwide. More efforts are needed to prevent stroke, and the findings from this study are a step in the right direction."

Explore further: Folic acid supplementation among adults with hypertension reduces risk of stroke

More information: Xiao Huang et al. Association between percent decline in serum total homocysteine and risk of first stroke, Neurology (2017). DOI: 10.1212/WNL.0000000000004648

Yong Huo et al. Efficacy of Folic Acid Therapy in Primary Prevention of Stroke Among Adults With Hypertension in China, JAMA (2015). DOI: 10.1001/jama.2015.2274

Related Stories

Folic acid supplementation among adults with hypertension reduces risk of stroke

March 15, 2015
In a study that included more than 20,000 adults in China with high blood pressure but without a history of stroke or heart attack, the combined use of the hypertension medication enalapril and folic acid, compared with enalapril ...

Greater benefit for pioglitazone in high-risk patients post stroke

September 19, 2017
(HealthDay)—For patients after an ischemic stroke or transient ischemic attack, pioglitazone is associated with greater benefit for those at higher risk for stroke or myocardial infarction (MI), according to a study published ...

Radioiodine therapy for thyroid cancer doesn't up stroke risk

August 21, 2017
(HealthDay)—Radioiodine (I-131) therapy for thyroid cancer is not associated with increased risk of stroke, according to a study published online Aug. 16 in Head & Neck.

Recommended for you

Heart researchers develop a new, promising imaging technique for cardiac arrhythmias

February 22, 2018
Every five minutes in Germany alone, a person dies of sudden cardiac arrest or fibrillation, the most common cause of death worldwide. This is partly due to the fact that doctors still do not fully understand exactly what ...

Scientists use color-coded tags to discover how heart cells develop

February 22, 2018
UCLA researchers used fluorescent colored proteins to trace how cardiomyocytes—cells in heart muscle that enable it to pump blood—are produced in mouse embryos. The findings could eventually lead to methods for regenerating ...

Beetroot juice supplements may help certain heart failure patients

February 22, 2018
Beetroot juice supplements may help enhance exercise capacity in patients with heart failure, according to a new proof-of-concept study. Exercise capacity is a key factor linked to these patients' quality of life and even ...

'Beetroot pill' could help save patients from kidney failure after heart X-ray

February 22, 2018
Beetroot may reduce the risk of kidney failure in patients having a heart x-ray, according to research led by Queen Mary University of London.

Women once considered low risk for heart disease show evidence of previous heart attack scars

February 20, 2018
Women who complain about chest pain often are reassured by their doctors that there is no reason to worry because their angiograms show that the women don't have blockages in the major heart arteries, a primary cause of heart ...

Can your cardiac device be hacked?

February 20, 2018
Medical devices, including cardiovascular implantable electronic devices could be at risk for hacking. In a paper publishing online today in the Journal of the American College of Cardiology, the American College of Cardiology's ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.