Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem

Background: Elevated plasma total homocysteine level has been associated wi th cardiovascular disease in many studies, mostly in Europe and North Ameri ca. Data on persons from other areas and on associations with overall morta lity are sparse. Objective: To determine the relation of plasma homocysteine level to all-ca use and cause-specific mortality. Design: Prospective observational study with 9- to 11-year follow-up. Setting: A free-living, multiethnic Jewish population in western Jerusalem, Israel. Participants: 1788 residents of Jerusalem (808 men and 980 women) who were at least 50 years of age and were examined between 1985 and 1987 as part of the Kiryat Yovel Community Health Study. Measurements: Nonfasting plasma homocysteine level was determined in frozen stored samples. Deaths during follow-up were identified by linkage with th e national population registry. Results: Plasma homocysteine levels exceeded 14 mu mol/L in 28% of men and 20% of women. During the study period, 405 deaths occurred. In multivariate Cox models that controlled for possible confounders, a nonmonotonic increa se in mortality hazard ratios was associated with ascending quintile of hom ocysteine level: 1.0, 1.4, 1.3, 1.5, and 2.0 (P < 0.001 for trend), The rel ation was similar for cardiovascular and noncardiovascular causes of death (excluding cancer). The association was weaker when deaths that occurred du ring the first 5 years of follow-up were excluded; corresponding hazard rat ios for ascending quintile of homocysteine level were 1.0, 1.0, 1.2, 1.1, a nd 1.6 (P = 0.063 for trend). Age- and sex-adjusted percentages of deaths " attributable" to elevated plasma homocysteine level(greater than or equal t o 14 mu mol/L) were 12.5% (95% CI, 6.7% to 18.8%)for all deaths, 16.0% (CI, 7.2% to 25.6%) for deaths during the first 5 years of follow-up, and 8.3% (CI, 1.5% to 16.1%) for later deaths. Conclusions: A mildly to moderately elevated nonfasting plasma homocysteine level is a substantial risk marker for death from all causes. The associat ion seems to be stronger during the first 5 years of follow-up.