A substance in the blood was linked with a higher chance of dying over the next decade—but the strength of that link depended partly on a person’s inherited biology. Homocysteine is an intermediate amino acid produced as the body breaks down methionine.

It can contribute to dysfunction in the blood vessel lining and is linked with hardened arteries and blood clots. The American Heart Association has recognized that elevated homocysteine levels are associated with an increased risk of stroke and other vascular events.

But the relationship between homocysteine concentrations and the risk of death remains limited and conflicting, especially for particular causes of death or populations. Earlier studies linked higher homocysteine with higher risks of death, yet pooled trials found that lowering homocysteine with folic acid or vitamin B did not improve those relationships.

Few prospective studies had examined homocysteine and the risk of death in the general Chinese population. Important gaps remained around inherited biology, surroundings, lifestyle, and nutrition. So this study examined the ten-year risk of death from any cause and cardiovascular death, and tested whether a particular inherited pattern changed the relationship.

Deaths were collected from national and municipal health records. The main outcome was death from any cause, while the second outcome was cardiovascular death. Follow-up ran from the starting assessment until a participant died or until the end of follow-up on thirty-first December twenty twenty-one.

During an average follow-up of nearly ten years, three hundred twenty deaths were documented, including one hundred seven cardiovascular deaths. The survival curves revealed a significant dose-response relationship between homocysteine and both all-cause and cardiovascular mortality.

After adjustment for other factors, people with homocysteine concentrations from ten to below fifteen had a seventy-four percent higher risk of death from any cause than people below ten. People with concentrations of fifteen or higher also had an increased risk of all-cause mortality, sixty-four percent higher than the reference group.

The inherited pattern changed the association between homocysteine and all-cause mortality. Elevated homocysteine was significantly associated with increased risk in people with the six-seven-seven C-C pattern. The association appeared stronger in several groups, but the interaction test for a trend was not significant.

The study supports a positive relationship between plasma homocysteine and ten-year all-cause and cardiovascular mortality in a community-based Chinese population. Elevated homocysteine was associated with increased all-cause mortality in people with the six-seven-seven C-C pattern, while the relationship faded in people with the C-T or T-T patterns.

What this means for an individual is still an open question: the biological mechanism and whether lowering homocysteine changes long-term mortality require further investigation. In this Chinese community population, higher homocysteine was associated with greater risk of death from any cause and from cardiovascular disease.

The association with all-cause death was strongest in people with one genetic pattern, not another.