Abstract
OBJECTIVE: This study aimed to investigate the relationship between serum vitamin D (Vit D) levels and the risk of mortality among adults with H-type hypertension, a subtype of hypertension characterized by elevated homocysteine (Hcy) levels. METHODS: This retrospective analysis utilized NHANES 2001 to 2006 to examine associations of Vit D and Hcy with mortality in hypertensive adults overall (n=5459), followed by targeted analyses in H-type hypertension (n=2276). The primary endpoints of the study were all-cause mortality and cardiovascular disease mortality, with follow-up through 2019. Weighted multivariable Cox models, mediation analyses, restricted cubic splines, and machine-learning validation were conducted. RESULTS: In the overall hypertensive cohort, H-type hypertension had lower Vit D and higher mortality than non-H-type. Higher Vit D was inversely associated with mortality. Joint risk analysis showed greater risk reduction with Vit D>50 nmol/L and Hcy<10 μmol/L than with either factor alone. Hcy was a mediating factor in the relationship between Vit D and mortality. In H-type hypertension, Vit D showed a linear inverse association with mortality. Vit D was identified as an important variable through LASSO regression for feature selection. Five machine learning models were constructed, and three of them performed well in predicting mortality. Among Vit D-deficient individuals with H-type hypertension, engagement in moderate to vigorous activity was associated with a reduced risk of mortality. CONCLUSION: Higher serum Vit D levels linked to lower mortality risk in hypertension patients, including H-type hypertension, with significantly higher risk in severe deficiency (<25 nmol/L).