The Interaction of Hypertension and Homocysteine Increases the Risk of Mortality Among Middle-aged and Older Population in the United States

Objectives: To investigate the interaction of hypertension and total plasma homocysteine (tHcy) levels on risk of all-cause and cardiovascular disease (CVD) mortality among middle-aged and older population.

Methods: This observational cohort study analyzed data from the National Health and Nutrition Examination Survey database (1999-2002 survey cycle). A generalized additive model (GAM) based on Cox proportional hazards models was applied to estimate the relationship of tHcy level with all-cause and CVD mortality. Stratification analyses by sex and renal function were performed.

Results: Among 5724 individuals aged 40-85, 704 (12.3%) died, with 339 CVD deaths after a median follow-up period of 5.58 years. Mean age was 60.7 ± 13.4 years (49.6% men). In the fully adjusted model, we found that per 1 μmol/l increment of plasma tHcy was associated with 8% increased risk of all-cause mortality and 7% increased risk of CVD mortality in hypertensive participants. The adjusted hazard ratio (95% CIs) for all-cause and CVD mortality were 1.08 (1.06-1.10) and 1.07 (1.04-1.10), respectively. There were pronounced interactive effects between hypertension and tHcy levels on risk of all-cause mortality (P for interaction = 0.031).

Conclusion: Hypertension and tHcy levels can interactively affect the risk of all-cause mortality among middle-aged and older population. Conceivably, hypertension may further enhance the ability of elevated tHcy to provoke the risk of all-cause mortality.